Computer-assisted Continuous Infusion Research Articles

Half-time or Half-life

Elimination half-life is the pharmacokinetic parameter used most commonly to describe duration of pharmacologic action, including that expected of intravenous anesthetic drugs administered by continuous infusion. Little consideration has been given, however, to the relevance of elimination half-life in describing plasma (central compartment) drug concentrations in the context of relevant infusion durations. Therefore, simulations were performed with multicompartment pharmacokinetic models for six intravenous anesthetic drugs. These models had elimination half-lives ranging from 111 to 577 min. The input in each simulation was in infusion regimen designed to maintain a constant plasma drug concentration for durations ranging from 1 min to 8 h and until steady state. The time required for the plasma drug concentration to decrease by 50% after terminating each infusion in each of the models was determined and was designated the "context-sensitive half-time," where "context" refers to infusion duration. The context-sensitive half-times were markedly different from their respective elimination half-lives and ranged from 1 to 306 min. The half-times were explained by posing each pharmacokinetic model in the form of a hydraulic model. These simulations demonstrate that elimination half-life is of no value in characterizing disposition of intravenous anesthetic drugs during dosing periods relevant to anesthesia. We propose that context-sensitive half-times are a useful descriptor of postinfusion central compartment kinetics.

Titration of the plasma effect site equilibrium rate constant of propofol; a link method of 'Concentration-Probability-Time'

BackgroundThe plasma effect-site equilibrium rate constant (ke0) of propofol has been reported in various pharmacodynamic studies; however, it is not desirable to apply ke0 for the link with pharmacokinetic models that were separately investigated. Thus, we titrated ke0 for the pharmacokinetic model, which is known as the multiple covariates adjusted model of propofol.MethodsNinety female patients scheduled for gynecologic surgery were randomly assigned to three groups targeting different plasma concentrations of 5.4, 8.1, and 10.8 µg/ml. Target-controlled infusions (TCI) were provided by a computer-assisted continuous infusion system. Time to loss of responsiveness (LOR) was measured by a blind investigator; effect-site concentrations (Ce) for LOR were then calculated with simulation of TCI using different ke0s. We determined the ke0 minimizing total discrepancy (TD) between the inputted and calculated ke0 from the t1/2ke0s for a given probability of LOR of the Ce, and also obtained the ke0 for the minimal TD between the median Ce, which were compared to the known ke0.ResultsKe0s from these two methods were 0.3692 and 0.3788/min. Ces for LOR with these ke0s were significantly different from those with Schnider's ke0.ConclusionsWe proposed a method for titration of the ke0 of propofol. The ke0s of propofol was lower than Schnider's ke0. An adequate ke0 for the specific pharmacokinetic model and a certain population would be useful for prediction of an accurate Ce, and could be used for calculation of accurate dosing during targeting of the effect site.

Proper Target Concentration of Fentanyl during Endotracheal Intubation with a CACI (Computer Assisted Continuous Infusion) in Patients Undergoing Coronary Artery Bypass Graft Surgery

Background: The computer-assisted continuous infusion (CACI) system was developed to more rapidly attain and to maintain stable effect-site fentanyl concentrations as compared with the intermittent injection method. The CACI system allows the anesthesiologist to control effect-site fentanyl concentrations during various surgical stimuli during cardiac anesthesia. This system can rapidly control the depth of anesthesia and compensate for the disadvantages of IV anesthesia. Early patient recovery also enables early tracheal extubation, which is an important component of the “fast track” cardiac surgery pathway. In this study, the use of a target-controlled infusion of low-dose propofol was combined with the target-controlled infusion of fentanyl for patients undergoing coronary artery bypass graft surgery. The purpose of this study was to evaluate the proper effect-site concentration of fentanyl for the tracheal intubation of patients undergoing coronary artery bypass graft surgery. Methods: Fifty patients scheduled for elective coronary artery bypass graft surgery were included, and randomly allocated to group L (effect-site fentanyl concentration = 5 ng/ml, n = 25) or group H (effect-site fentanyl concentration = 7.5 ng/ml, n = 25). Anesthesia was induced and maintained by the computer-controlled infusions of propofol and fentanyl. Hemodynamics and other variables were recorded preinduction, and before and 1 minute after intubation. Results: The two groups were compared with regard to demographic and perioperative data. The two groups were similar demographically, and no significant differences was found in any hemodynamic parameter at any time between the two groups. Conclusions: Both fentanyl regimens provided stable hemodynamics and adequate anesthesia in patients during endotracheal intubation. It is reasonable to say that the lower dose of fentanyl (5 ng/ml) may be the better choice, because it provides the same level of anesthesia during endotracheal intubation during coronary artery bypass graft surgery.

THIS MONTH IN ANESTHESIOLOGY

THIS MONTH IN ANESTHESIOLOGY

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. Preanesthetic medication with 5 microg/kg oral clonidine, but not 2.5 microg/kg clonidine, is associated with prolonged recovery from propofol/fentanyl anesthesia.

Bispectral analysis during cardiopulmonary bypass: the effect of hypothermia on the hypnotic state

Study Objective: To evaluate the hypothesis that the bispectral index (BIS) is not affected by the hypothermia that is associated with cardiopulmonary bypass (CPB). Design: Prospective, observational study. Setting: Cardiac surgical operating suite of a university medical center. Patients: 100 patients undergoing cardiac surgery requiring CPB. Interventions: A constant effect site concentration of 2.2 ng/mL for fentanyl and 60 ng/mL for midazolam was maintained throughout surgery using a computer-assisted continuous infusion technique. Measurements: The BIS value, percent isoflurane administered, predicted brain concentrations of midazolam and fentanyl, and nasopharyngeal temperature were recorded before CPB, at 15 minutes after the onset of CPB, at placement of the aortic cross-clamp, at start of rewarming, on separation from CPB, and 15 minutes after the end of CPB. Data were analyzed using a repeated-measures mixed-effects method, taking into account temperature, age, and predicted level of each anesthetic. Main Results: A significant overall association between temperature and BIS was observed independent of patient age, predicted brain midazolam or fentanyl concentration, percent isoflurane administered, and surgical time point (p < 0.001). The BIS is estimated to decrease by 1.12 units for each degree Celsius decrease in body temperature. Conclusions: Hypothermia decreases the BIS by 1.12 units per degree Celsius decline in temperature.

Does sufentanil concentration influence isoflurane requirements during coronary artery bypass grafting?

Objective: To search for concentration-related suppression of hemodynamic responsiveness by sufentanil. Design: Prospective, randomized, double-blind study. Setting: University hospital. Participants: Patients undergoing elective coronary artery bypass grafting (CABG). Intervention: Patients were assigned to target effect-site sufentanil concentrations of 1.5 ng/mL (group L; n = 14), 3.0 ng/mL (group M; n = 13), or 4.5 ng/mL (group H; n = 12). Sufentanil was administered by computer-assisted continuous infusion. Isoflurane was used to maintain intraoperative hemodynamics near preoperative values. Measurements and Main Results: Hemodynamics, the electroencephalographic spectral edge (SE 95), and end-tidal isoflurane concentration (ET-ISO) were measured every 10 to 30 seconds during the prebypass period. Serum sufentanil concentration was measured at intervals. Prebypass serum sufentanil concentrations were stable, averaging 3.0 ± 0.7, 5.1 ± 1.1, and 7.1 ± 1.3 ng/mL in groups L, M, and H, respectively. The groups did not differ with respect to the speed of induction, intraoperative hemodynamics, incidence of isoflurane use, or isoflurane concentrations required. ET-ISO and serum sufentanil levels were not correlated. Among seven group L patients who did not require isoflurane, the average prebypass serum sufentanil concentration ranged from 1.7 to 3.3 ng/mL. Conclusion: Sufentanil does not induce concentration-related suppression of hemodynamic responsiveness over the range studied. A stable serum sufentanil concentration of 3.0 ± 0.7 ng/mL induces the maximal opioid effect and need not be exceeded in patients undergoing CABG. A sufentanil concentration of 1.7 ng/mL provides clinically adequate anesthesia without supplementation in some premedicated patients undergoing CABG.

This Month in ANESTHESIOLOGY

This Month in ANESTHESIOLOGY

Determination of plasma concentrations of propofol associated with 50% reduction in postoperative nausea.

Subhypnotic doses of propofol possess direct antiemetic properties. The authors sought to determine the plasma concentration of propofol needed to effectively manage postoperative nausea and vomiting. Patients aged 18-70 yr who were classified as American Society of Anesthesiologists physical status 1 or 2 and had surgery during general anesthesia were approached for the study. Only patients who had nausea (verbal rating score > 5 on a 0- to 10-point scale), retching, or vomiting in the postanesthetic care unit participated. Propofol was administered to these patients to achieve target plasma concentrations of 100, 200, 400, and 800 ng/ml using a computer-assisted continuous infusion device. Target concentrations were increased every 15 min until patients described at least a 50% reduction in symptoms on the verbal rating score. An arterial blood sample was obtained at each step. The measured plasma propofol concentrations were used to analyze data. Blood pressure, heart and respiratory rates, arterial blood saturation, sedation score, and overall satisfaction with treatment were recorded. Of the 89 patients who consented to the study, 15 patients met entry criteria and were enrolled. Five of these patients also had retching or vomiting when they entered the study. Fourteen patients responded successfully to treatment. One patient did not achieve the required response at plasma concentrations of 830 ng/ml. Hence the success rate for the treatment of postoperative nausea and vomiting was 93%. Among patients who responded, the median plasma concentration associated with an antiemetic response was 343 ng/ml. There was no difference in sedation scores from baseline and no episodes of desaturation. Hemodynamic parameters were stable during the study. Propofol is generally efficacious in treating postoperative nausea and vomiting at plasma concentrations that do not produce increased sedation. Simulations indicate that to achieve antiemetic plasma propofol concentrations of 343 ng/ml, a bolus dose of 10 mg followed by an infusion of approximately 10 microg x kg(-1) x min(-1) are necessary.

Reduction by fentanyl of the Cp50 values of propofol and hemodynamic responses to various noxious stimuli.

Propofol and fentanyl infusion rates should be varied according to the patient's responsiveness to stimulation to maintain satisfactory anesthetic and operative conditions. However, somatic and autonomic responses to various noxious stimuli have not been investigated systematically for intravenous propofol and fentanyl anesthesia. Propofol and fentanyl were administered via computer-assisted continuous infusion to provide stable concentrations and to allow equilibration between plasma-blood and effect-site concentrations. The propofol concentrations needed to suppress eye opening to verbal command and motor responses after 50-Hz electric tetanic stimulation, laryngoscopy, tracheal intubation, and skin incision in 50% or 95% of patients (Cp50 and Cp95) were determined at fentanyl concentrations of 0.0, 1.0, 2.0, 3.0, and 4.0 ng/ml in 133 patients undergoing lower abdominal surgery. The ability of propofol with fentanyl to suppress hemodynamic reactions in response to various noxious stimuli also was evaluated by measuring arterial blood pressure and heart rate before and after stimulation. The various Cp50 values for propofol alone (no fentanyl) for the various stimuli increased in the following order: Cp50loss of consciousness, 4.4 microg/ml (range, 3.8-5.0); Cp50tetanus, 9.3 microg/ml (range, 8.3-10.4); Cp50laryngoscopy, 9.8 microg/ml (range, 8.9-10.8); Cp50skin incision, 10.0 microg/ml (range, 8.1-12.2); and Cp50intubation, 17.4 microg/ml (range, 15.1-20.1; 95% confidence interval). The reduction of Cp50loss of consciousness, with fentanyl was minimal; 11% at 1 ng/ml of fentanyl and 17% at 3 ng/ml of fentanyl. A plasma fentanyl concentration of 1 ng/ml (3 ng/ml) resulted in a 31-34% (50-55%) reduction of the propofol Cp50s for tetanus, laryngoscopy, intubation, and skin incision. Propofol alone depresses prestimulation blood pressure but had no influence on the magnitude blood pressure or heart rate increase to stimulation. Propofol used with fentanyl attenuated the systolic blood pressure increases to various noxious stimuli in a dose-dependent fashion. The authors successfully defined the propofol concentration required for various stimuli. Tracheal intubation was the strongest stimulus. The absence of somatic reactions for propofol does not guarantee hemodynamic stability without fentanyl. Propofol with fentanyl was able to suppress motor and hemodynamic reactions to various noxious stimuli.

Performance of Computer-Assisted Continuous Infusion at Low Concentrations of Intravenous Sedatives

Performance of Computer-Assisted Continuous Infusion at Low Concentrations of Intravenous Sedatives

A.103 Computer-assisted continuous infusion of low-dose propofol and sufentanil for mitral valve surgery: the fast track infusion?

A.103 Computer-assisted continuous infusion of low-dose propofol and sufentanil for mitral valve surgery: the fast track infusion?

The Interaction of Fentanyl on the Cp50 of Propofol for Loss of Consciousness and Skin Incision

We have previously demonstrated that the minimum alveolar concentration of isoflurane at 1 atm that is required to prevent movement in 50% of patients or animals exposed to a maximal noxious stimulus is markedly reduced by increasing fentanyl concentrations. Total intravenous anesthesia with propofol is increasing in popularity, yet the propofol concentrations required for total intravenous anesthesia or the interaction between propofol and fentanyl have not yet been defined. Propofol and fentanyl were administered via computer-assisted continuous infusion to provide pseudo-steady-state concentrations and allow equilibration between plasma-blood concentration and their biophase concentration. For the induction of anesthesia patients were randomly allocated to receive propofol only or propofol plus fentanyl 0.2, 0.8, 1.5, 3.0, and 4.5 ng/ml. In each group patients were randomized to target propofol concentrations of 1.5-10 micrograms/ml. At 7 and 10 min arterial blood samples were taken for subsequent measurement of propofol and fentanyl concentrations. At 10 min loss of consciousness was assessed by the patients' ability to respond to a simple verbal command. Thereafter a new target concentration of propofol was entered to ensure loss of consciousness, and succinylcholine was administered to facilitate tracheal intubation. Patients were rerandomized to a new target concentration of propofol (1-19 micrograms/ml) until skin incision. Before skin incision and 1 min after skin incision, arterial blood samples were again obtained for subsequent measurement of fentanyl and propofol concentrations. At skin incision and for 1 min the patient was observed for purposeful movement. Only samples in which the pre- and poststimulus drug concentrations were within 35% of each other were included. The propofol blood concentration at which 50% or 95% of patients did not respond to verbal command (Cp50s and Cp95s, respectively) and to skin incision (Cp50i and Cp95i, respectively), were calculated by logistic regression. There were 56 evaluable patients for calculating the propofol Cp50s and 53 patients for calculating the propofol Cp50i. For propofol alone the Cp50s was 3.3 micrograms/ml and the Cp95s 5.4 microgram/ml. Increasing fentanyl concentrations reduced the Cp50s (P = 0.03), and increasing age decreased the Cp50s (P = 0.04). For propofol alone the Cp50i was 15.2 (95% confidence interval 7.6-22.8) micrograms/ml and the Cp95i 27.4 micrograms/ml. Increasing fentanyl concentrations markedly reduced the Cp50i (P < 0.01), with a 50% reduction in Cp50i produced by 0.63 ng/ml fentanyl. The propofol Cp50i was decreased by 63% with 1 ng/ml fentanyl and 89% by 3 ng/ml fentanyl. At higher fentanyl concentrations the decrease in Cp50i was proportionally less, demonstrating a ceiling effect. We defined the propofol concentration required for loss of consciousness and showed that it is reduced by increasing fentanyl concentration and by increasing age. The propofol concentration (alone) adequate for skin incision is high but is markedly reduced by fentanyl. A ceiling effect in the Cp50i for propofol is seen with fentanyl concentrations greater than 3 ng/ml.

A rule-based postoperative pain controller: Simulation results

We describe a system for controlling postoperative pain, a phenomenon that is difficult to treat by conventional control methods due to interpatient variability, interferences, non-linearity and the lack of a plausible, well-defined mathematical model. The system consists of two phases. In Phase 1 a closed-loop fuzzy controller implementing a suitable control strategy brings the patient to a zero-pain state. In Phase 2, an open-loop computer-assisted continuous infusion controller maintains a constant concentration of the analgesic (alfentanil) in plasma, subject to an upper safety limit on infusion rate; the setpoint of this controller is periodically revised (either maintained or reduced) on the basis of feedback on the duration of zero pain (setpoint reduction is necessary because the open-loop system has no means of knowing whether analgesic is accumulating in the patient). Pain is quantified by the patient on a numerical scale of 1 to 10 at 1.5-min intervals during Phase 1 and 9-min intervals during Phase 2. In simulation trials in which a fixed approximate model was used for the effect of sedation on pain while the pharmacokinetics of alfentanil were varied from one simulated patient to another, zero pain was achieved in under 15 min with minimal overshoot in plasma drug concentration and was maintained, with only minor deviation, by means of low drug concentrations.

Midazolam and fentanyl continuous infusion anesthesia for cardiac surgery: comparison of computer-assisted versus manual infusion systems

Continuous infusion of intravenous anesthetics can be achieved either by a manually controlled infusion (MCI) pump, or by a computer-assisted continuous infusion (CACI) pharmacokinetic model-driven infusion system. Randomized double-blind comparisons of the two infusion systems for general anesthesia were performed in 24 patients undergoing coronary artery bypass grafting. Patients were allocated to receive continuous infusions of midazolam and fentanyl by either a MCI device or CACI. Midazolam and fentanyl infusions were independently titrated to maintain hemodynamic stability, defined as mean arterial pressure (MAP) and heart rate (HR) within 20% of baseline values. As directed by the study design, comparable hemodynamic control was achieved in both groups. Mean plasma fentanyl concentrations measured at specific timepoints were similar between groups. The plasma midazolam level for induction was 196 ± 139 ng/mL in the CACI group and 300 ± 128 ng/mL in the MCI group, and the fentanyl level was similar in both groups, 6.7 ± 1.9 ng/mL in CACI and 6.3 ± 4.6 ng/mL in the MCI group. The drug levels were lower ( P < 0.05) for midazolam during maintenance of anesthesia and similar for fentanyl during the maintenance of anesthesia. In the MCI group, the average duration of anesthesia was 246.5 ± 35.0 minutes, with a mean total fentanyl dose of 30.27 ± 11.14 μg/kg. In the CACI group, the average duration of anesthesia was 230.8 ± 44.1 minutes, with a mean total fentanyl dose of 34.61 ± 5.40 μg/kg ( P > 0.05 for comparisons between groups for duration of anesthesia and total fentanyl dose). Mean plasma midazolam concentrations measured at specific timepoints, and total amount of midazolam delivered per case, were significantly lower with CACI (mean total midazolam dose: CACI = 191.85 ± 49.51 μg/kg, MCI = 267.79 ± 84.22 μg/kg; P < 0.05). Furthermore, variability in plasma fentanyl and midazolam concentrations was significantly greater in the group receiving manually controlled infusions. It is concluded that CACI and MCI provided excellent hemodynamic stability with opioid drug concentrations lower than techniques based on fentanyl alone. The CACI method achieved more precise plasma concentrations, but both methods of drug delivery produced relatively similar plasma concentrations despite the very different dosing concepts.

Plasma Concentration of Fentanyl, with 70% Nitrous Oxide, to Prevent Movement at Skin Incision

The Cp50 (minimal steady state plasma concentration of an intravenous analgesic/anesthetic required to prevent a somatic response in 50% of patients following skin incision) and the Cp50-BAR (minimal plasma concentration of an analgesic/anesthetic required to prevent either a somatic, hemodynamic, or autonomic response in 50% of patients following skin incision) have been recently proposed as a measure, like minimum alveolar concentration (MAC; and MAC-BAR), to establish the relative potency of intravenous analgesics. This study was conducted to establish the Cp50 for fentanyl. Unpremedicated patients were administered fentanyl (in the presence of 70% N2O) via computer-assisted continuous infusion, a pharmacokinetic model-driven infusion device. After induction of anesthesia with fentanyl, the randomized target fentanyl concentration was entered into computer-assisted continuous infusion. This target fentanyl concentration was maintained until skin incision. Before induction, prior to skin incision, and immediately after skin incision, arterial blood samples were obtained for measurement of fentanyl and norepinephrine concentrations. At skin incision, patients were observed for a somatic, hemodynamic, or autonomic response. Only patients in whom the pre- and postincision fentanyl concentrations were within +/- 30% were included in the calculation of the Cp50. The Cp50 was calculated using logistic regression. The Cp50 for fentanyl was 3.26 ng/ml, and the Cp50-BAR was 4.17 ng/ml. Comparing these results with the previously published Cp50 of alfentanil, the potency of fentanyl relative to alfentanil is 1:58. Establishing the Cp50, once effect site equilibration has occurred, will allow pharmacodynamic comparisons between the opioids at equipotent concentrations.

Computerized Continuous Infusion of Intravenous Anesthetic Drugs During Pediatric Cardiac Surgery

We evaluated the efficacy of a computer-assisted continuous infusion device (CACI) using a two-drug infusion of midazolam and sufentanil as an anesthetic technique during pediatric cardiac surgery. Seventeen pediatric patients were anesthetized with CACI using age-appropriate pharmacokinetic models for administering sufentanil and midazolam. Predicted CACI plasma concentrations were correlated with assayed plasma drug concentrations at eight predefined intervals. The accuracy was assessed using median absolute prediction error. We found that plasma levels predicted by CACI provided a reasonable approximation of measured plasma concentrations for both drugs. The median absolute prediction error for sufentanil during cardiopulmonary bypass was compared with measurements made off of cardiopulmonary bypass (both pre and post cardiopulmonary bypass) and were 49% and 32%, respectively, and for midazolam 44% and 32%, respectively. We conclude that (a) current kinetic models provide a reasonable estimate of plasma drug concentrations, and (b) the ease of administration and targeted plasma level provided by the CACI system is an alternative to inhalation anesthesia using calibrated vaporizers.

Pharmacokinetic Model-driven Infusion of Fentanyl

Computer-assisted continuous infusion (CACI) is a pharmacokinetic model-driven infusion device that enables physicians to administer intravenous (iv) drugs in a quantitative fashion, specifying a theoretical blood or plasma concentration. This study evaluated the accuracy of CACI administration of fentanyl using a newly developed CACI device programmed with a well-known set of pharmacokinetic parameters for fentanyl. Patients received diazepam 1 or 2 h before surgery. Anesthesia was induced by a combination of 70% N2O and fentanyl administered by CACI to a predicted concentration of 15-25 ng.ml-1. After neuromuscular blockade and tracheal intubation, the desired plasma fentanyl concentration (setpoint) entered into CACI was 3-6 ng.ml-1, and then the setpoint fentanyl concentration was titrated according to strict criteria of adequate or inadequate anesthesia. Plasma samples for subsequent assay of fentanyl concentration then were taken: at predefined stimuli, when inadequate anesthesia occurred, or 5 min before an anticipated decrease in the fentanyl setpoint. The predictive accuracy of CACI was assessed by calculating for each patient the tenth, 50th, and 90th percentile of the performance error and absolute performance error from each measured and predicted plasma sample pair. Cumulative probability functions for each of these were then plotted. Precision was defined as the dispersion of the tenth to 90th percentile of the median percent performance error for the population and was found to be -31-26%. The median population performance error was -4%, and the median population absolute performance error was 21%.(ABSTRACT TRUNCATED AT 250 WORDS)

A Further Note on Computer-assisted Continuous Infusion

A Further Note on Computer-assisted Continuous Infusion

Sufentanil disposition during cardiopulmonary bypass.

In order to investigate the ability of a computer-assisted continuous infusion (CACI) system to maintain constant plasma levels of sufentanil during cardiopulmonary bypass (CPB) using pharmacokinetic data derived from healthy surgical patients to determine the infusion rate, ten patients were anaesthetized with diazepam, enflurane and oxygen until ten minutes prior to the expected time of initiation of CPB. At that point, an infusion of sufentanil, aimed to reach a central compartment concentration of 5 ng.ml-1, was started via CACI. Plasma concentrations of sufentanil, haematocrit, total protein and albumin concentrations, and nasopharyngeal and CPB inflow temperatures were obtained at predetermined intervals before and up to 90 min after the initiation of CPB. Plasma concentrations of sufentanil reached 3.8 +/- 0.4 ng.ml-1 before CPB and approached the 5.0 ng.ml-1 set point (4.7 +/- 0.4 ng.ml-1) over the 90 min of CPB. In conclusion, our results show that it is possible to obtain stable plasma levels of sufentanil on CPB using a pharmacokinetically driven infusion scheme; however, our data suggest that use of such a system may lead to accumulation of drug during CPB.