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Anesth Analg 2008; 106:1207-1214
© 2008 International Anesthesia Research Society
doi: 10.1213/ane.0b013e31816782ff
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TECHNOLOGY, COMPUTING, AND SIMULATION

The Predictive Performance of a Pharmacokinetic Model for Manually Adjusted Infusion of Liquid Sevofluorane for Use with the Anesthetic-Conserving Device (AnaConDa): A Clinical Study

Javier F. Belda, MD, PhD*, Marina Soro, MD, PhD{dagger}, Rafael Badenes, MD{dagger}, Andreas Meiser, MD, PhD{ddagger}, María Luisa García, MD{dagger}, Gerardo Aguilar, MD, PhD{dagger}, and Francisco J. Martí, MD, PhD{dagger}

From the *Department of Anesthesiology and Intensive Care, Hospital Clínico Universitario de Valencia, Valencia, Spain; {dagger}Department of Anesthesiology and Intensive Care, Hospital Clínico Universitario, Valencia, Spain; and {ddagger}Klinik fur Anaesthesiologie, St. Josef-Hospital, Klinikum der Ruhr-Universitat, Bochum, Germany.

Address correspondence and reprint requests to F. Javier Belda, MD, PhD, Anesthesiology and Intensive Care Department, Hospital Clínico Universitario de Valencia, Avenida Blasco Ibáñez, 17. 46010 Valencia, Spain. Address e-mail to fjbelda{at}uv.es.


   Abstract
Top
 Abstract
Introduction
 METHODS
 RESULTS
 DISCUSSION
 Appendix 2
 REFERENCES
 
BACKGROUND: The Anesthetic-Conserving Device (AnaConDa) can be used to administer inhaled anesthetics using an intensive care unit (ICU) ventilator. We evaluated the predictive performance of a simple manually adjusted pump infusion scheme, for infusion of liquid sevoflurane to the AnaConDa.

METHODS: We studied 50 ICU patients who received sevoflurane via the AnaConDa. They were randomly divided into three groups. A 6-h infusion of liquid anesthetic was adjusted according to the infusion scheme to a target end-tidal sevoflurane concentration of 1% (Group 1%, n = 15) and 1.5% (Group 1.5%, n = 15). The initial rate was adjusted to reach the target concentration in 10 min and then the infusion was reduced to the first hour maintenance rate and readjusted once each hour afterwards. The actual concentrations were measured in the breathing circuit and compared with the target values. In the third group (n = 20) we used the model to increase and decrease the target concentration (±0.3%) for 3 h and evaluated the actual change in concentration achieved. The ability of the infusion scheme to provide the target concentration was quantified by calculating the performance error (PE). Infusion scheme performance was evaluated in terms of accuracy (median absolute PE, MDAPE) and bias (median PE, MDPE).

RESULTS: Performance parameters (mean ± sd, %) were for 1%, 1.5%, increase of concentration by 0.3% and decrease of concentration by 0.3% groups, respectively: MDAPE 5.3 ± 5.5, 2.6 ± 4.0, 5.0 ± 5.6, 5.5 ± 5.4; MDPE –5.3 ± 5.5, –2.3 ± 4.1, –0.1 ± 7.1, 0.2 ± 5.4. No significant differences were found between means of all performance parameters when the 1% and 1.5% groups were compared.

CONCLUSIONS: There is an excellent 6-h predictive performance of a simplified pharmacokinetic model for manually adjusted infusion of liquid sevoflurane when using the AnaConDa to deliver sevoflurane to ICU patients.


   Introduction
Top
 Abstract
 Introduction
METHODS
 RESULTS
 DISCUSSION
 Appendix 2
 REFERENCES
 
Sedation is an essential aspect of patient care in the intensive care unit (ICU), as it reduces the reaction to stress, prevents anxiety, increases comfort, improves tolerance to mechanical ventilation, and makes nursing care easier.1,2 In addition, amnesia produced by sedatives may reduce the serious long-term psychological disorders observed in 15% of patients in these units.3–7

Most commonly, IV drugs are used for ICU sedation.8–18 However, inhaled anesthetics may be ideal sedatives for the ICU14–20 because of their pulmonary elimination, limited amount of metabolism, bronchodilation,20 and cardioprotective effects.21–23

However, inhaled anesthetics are not widely used for sedation in the ICU, since most modern ICU ventilators do not readily accommodate an anesthetic vaporizer. The new anesthetic conserving device (ACD), AnaConDa (Sedana MedicalTM, Sweden),24–26 uses a syringe pump to deliver inhaled anesthetic in liquid form into the breathing circuit of a standard ICU ventilator (Fig. 1).27 A main advantage when compared with an ICU ventilator (open circuit) with a vaporizer attached is that an ACD has been proven to reduce anesthetic consumption24 to a level equivalent to that of a circle system using a fresh gas flow of 1.5 L/min.24,26 The manufacturer of the device recommends an infusion scheme whereby an initial rate is used to achieve the desired concentration followed by a reduced infusion rate to maintain the desired concentration. This recommended approach does not model the known characteristics of uptake and distribution for inhaled anesthetics. A precise infusion scheme for the syringe pump ensuring the desired alveolar concentration of the inhaled anesthetic has not yet been described.


Figure 126
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  		Figure 1. Cross-sectional view of the anesthetic conserving device (ACD, AnaConDa). From Sackey et al.,27 with permission.

 

We adapted a classical pharmacokinetic model to obtain an infusion scheme for the clinical use of the ACD with sevoflurane. Since the infusion rate of the pump was manually adjusted, a key objective was to make only one infusion rate change per hour, to facilitate its clinical use. Moreover, when a change in concentration was desired, this scheme needed to facilitate increasing or decreasing the target concentration when necessary.

We evaluated the predictive performance in patients of a simple, manually adjusted pump infusion scheme for continuous infusion of liquid sevoflurane to an ACD filter for 6 h with the goal of maintaining a constant targeted alveolar concentration. Performance was analyzed after a standard method described by Varvel et al.,28 which has been extensively used to evaluate the predictive capacity of IV target-controlled infusion systems29 and the accuracy of models of volatile anesthetic uptake.30–32


   METHODS
Top
 Abstract
 Introduction
 METHODS
RESULTS
 DISCUSSION
 Appendix 2
 REFERENCES
 
The hospital ethics committee approved the study and informed consent was obtained from all patients during the preoperative assessment. Fifty adult patients admitted to the ICU after major surgical interventions under total IV anesthesia were studied. In the postoperative period, all patients received sevoflurane via the ACD. Thirty patients received sevoflurane for 6 h. They were randomly divided into two groups of 15 patients in which the infusion rate was adjusted after the specific pharmacokinetic model (see below), so that the 1% (Group 1%) and 1.5% (Group 1.5%) alveolar target concentrations of sevoflurane were reached.

In order to study the capacity of the model to increase and decrease (±0.3%) the target concentration, another 20 patients (Group rise/low 0.3%) with similar characteristics were studied. This group received sevoflurane for 3 h.

Patients with respiratory diseases, high ventilatory demands, hemodynamic instability or obesity (20% over their ideal weight) were excluded.

Study Protocol
Patients were sedated and mechanically ventilated with different ICU ventilators. Respiratory patterns were adjusted according to the patients’ needs, to obtain normocapnia (PAco2 ranging from 35 to 45 mm Hg). The Pao2/Fio2 ratio was over 300 mm Hg for all cases and positive end-expiratory pressure was adjusted between 5 and 10 cm H2O. Electrocardiogram leads and hemodynamic variables were monitored by means of a Tramscope monitor (MarquetteTM, Milwakee). A Bispectral Index 2000 monitor (BIS, Aspect Medical SystemsTM, MA) was used to evaluate the sedation level. At the ventilator’s expiratory port a scavenging system was adapted and connected to the central vacuum terminal (Scat, TemelTM, Spain).

At the beginning of the study, all patients were sedated with continuous IV propofol and remifentanil infusions to achieve BIS values between 55 and 65. The ACD was fitted between the Y piece of the respiratory circuit and the endotracheal tube. The sampling line of the gas monitor (Vamos, DragerTM, Lubeck, Germany) was connected to the sampling port of the ACD and the sampling flow (150 mL/min) was redirected to the breathing system on the patient side of the ACD. At that point, propofol administration was stopped. The sevoflurane infusion started when a stable BIS value equal or superior to 80 had been observed for at least 5 min (with an index of signal quality of 80%–100%), which corresponded clinically to a Ramsay score 2–3.33 For sevoflurane infusion to the ACD, a syringe infusion pump Ivac P7000 (Alaris Medical SystemsTM, UK) was used. The pump’s infusion rate was adjusted following the values obtained from the pharmacokinetic model (see model below). The initial rate was designed to reach the alveolar target concentration in 10 min. At that point, infusion rate was reduced to the first hour maintenance rate. The infusion rate was readjusted just once each hour until the study’s 6-H period elapsed.

In the 20 patients for whom the increases and decreases of concentration were performed, the initial target of end-tidal (ET) sevoflurane was 0.7%. After 75 min, following the same model, the infusion rate was adjusted to produce an increase in concentration of 0.3% within 5 min. At minute 120, following the same pharmacokinetic scheme, the infusion rate was stopped for a specified time to decrease the ET concentration by 0.3% and was then restarted to maintain this concentration for another 60 min. Hemodynamic data and ET sevoflurane concentration values were recorded at minute 10 and every 5 min afterwards in all patients.

Model for Sevoflurane Administration
To produce a guide for liquid anesthetic infusion with the ACD, we designed a pharmacokinetic model that included two components: the patient’s anesthetic uptake and the loss of anesthetic through the ACD. Anesthetic uptake and distribution was modeled with a nine-compartment model based on that described by Lowe34 and subsequently modified by Heffernan et al.35,36 and Kennedy and Baker.37 Several schemes for direct injection of liquid anesthetics into a closed circuit following the method of Lowe or the square-root-of-time model have been evaluated.38–41 However, our model is simpler because an open-circuit ventilator is used instead of an anesthetic breathing circular circuit. As a result, the circuit compartment can be disregarded and neither rebreathing nor fresh gas flow need to be considered. Other assumptions regarding cardiac output (CO), lung volumes, ventilation, and gas uptake are described in detail in the Appendix 1 (available at www.anesthesia-analgesia.org). An empirical formula was used to adjust for the loss of anesthetic through the filter (Appendix 1).

The model was implemented using an Excel spreadsheet. When patient weight, sevoflurane target concentration, minute ventilation and induction time are entered into the "patient data and settings" box, both initial and maintenance infusion rate are calculated and displayed in the cells of the bottom right-hand box (Table 1).


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  		Table 1. Pharmacokinetic Model for Sevoflurane Infusion to Anesthetic Conserving Device (ACD) Filter (Excel spreadsheet, see Appendix 1 and on-line supplement)

 


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  		Table 1. Continued

 
To alter the alveolar concentration of sevoflurane, the increase or decrease desired is entered into the specified cells at the bottom of the spreadsheet. To provide an increase in ET concentration, the program calculates the required increase of infusion rate to be performed for exactly 5 min, and the subsequent maintenance rate. To provide a decrease, the program calculates the time period in minutes for which the syringe pump must be stopped and the subsequent maintenance rate afterwards (Table 1).

Computation of Performance Parameters
Performance parameters were determined following the methods described by Varvel et al.28 and used in many studies of target-controlled IV anesthesia.29,30,42,43 The basic estimation of the accuracy of each measurement (against the target) is the performance error (PE) calculated as the difference between the measured concentration (Cm) and the predicted (target) concentration (Cp) related to the predicted concentration:



Formula 1

This way in an ideal system Cm and Cp are equal and PE is zero %.

From the PE at each time-point, two basic parameters are calculated: (1) The median absolute PE (MDAPE, %) which is the median of the absolute values of PE. This MDAPE reflects the precision of the model and is the single best predictor of clinical acceptability of the performance of the model. For example, a MDAPE of 10% indicates that the median of the obtained values will be 10% above or below the target. This way an ideal MDAPE would be zero %. (2) The median PE (MDPE, %) is the median of the sometimes positive and other time negative values of PE. It measures bias which may be above or below the target. For example, a negative MDAPE (i.e., –6%) indicates that the median of the obtained values will be below the target, disregarding its absolute value which is expressed by the MDAPE. Therefore, MDAPE (precision) and MDPE (bias) are the main parameters used to determine the model’s predictive performance in a single patient (intrasubject analysis). For modeling performance in a group of patients, the mean value (and standard deviation) of the individual values of each parameter can be taken ("two-stage approach"). This way, all patients are equally weighed. In addition, a "pooled data approach" was also performed. This method uses all of the measurements from all individuals as if they came from one "average" individual.

Statistical Analysis
All analyses were performed using descriptive statistics from SPSS for Windows (version 11.0, SPSSTM, Chicago, IL). Two-stage analysis values are shown as mean, standard deviation, and confidence interval of 95%. For the pooled data analysis, median, minimum, and maximum values are shown. Box and whisker plots indicate median, 25th and 75th percentile (box), 5th and 95th percentile (whisker), and outlier values. Mann–Whitney’s U test for independent samples was used to test the difference between the means of MDAPE and MDPE at each target concentration for both 6-h as well as the rise and lower results. P < 0.05 was considered statistically significant.


   RESULTS
Top
 Abstract
 Introduction
 METHODS
 RESULTS
DISCUSSION
 Appendix 2
 REFERENCES
 
Fifty patients consented to participate. Demographic data are shown in Table 2.


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  		Table 2. Demographic and Surgical Characteristics

 

The performance accuracies of the model with the two-stage approach for the 6 h sedation are shown in Table 3. The results of the pooled data approach can be seen in Figure 2. Figure 3 shows the time course of PE for all cases during the 6-h period. Except for occasional transients, PEs for all cases were between –25% and +25%. No statistically significant differences were found between the means of all performance parameters when compared at the studied concentrations. This means that the predictive performance of the model is the same for the different target sevoflurane concentrations studied.


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  		Table 3. Mean Performance Parameters for 6 h

 

Figure 226
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  		Figure 2. Box and whisker plots indicating median, 25th and 75th percentile (box), 5th and 95th percentile (whiskers), and outlier values for median absolute performance error (APE, accuracy), median PE (PE, bias) of hand-driven continuous infusion of liquid sevoflurane to the AnaConDa device during the 6-h analysis in the 1% and 1.5% groups. Performance parameters were not significantly different among concentrations (P < 0.05 by one-way nonparametric analysis of variance).

 

Figure 326
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  		Figure 3. Performance error (PE) for all 30 cases (Groups 1 and 1.5%) plotted against time during the 6-h analysis. This plot allows the performance of the model in each patient and in the group to be visualized, providing a graphical representation of the bias and time-weighted variability.

 

The performance accuracy of the model and the results of the two-stage approach when it is adjusted to increase or decrease the alveolar concentration are shown in Table 4 and the time course of PE for all these patients is shown in Figure 4. Except for occasional transients, PEs for all cases were between ±20%.


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  		Table 4. Mean Performance Parameters for the Low Initial Concentration, Rise and Lower

 

Figure 426
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  		Figure 4. Performance error (PE) for the Rise/Low 0.3% group, plotted against time during the 3-h analysis. This plot allows the performance accuracy of the model when it is adjusted to increase or decrease the alveolar concentration, providing a graphical representation of the bias and time-weighted variability.

 

Changes in mean arterial blood pressure and heart rate were below 10% of control values in all patients, and thus there was no need to modify the infusion rate based upon hemodynamic changes.


   DISCUSSION
Top
 Abstract
 Introduction
 METHODS
 RESULTS
 DISCUSSION
Appendix 2
 REFERENCES
 
This study evaluated the accuracy of a dosing scheme to achieve, maintain, and change different sevoflurane concentrations via the ACD at the bedside in ICU patients.

The model was intended as a simple guide to manually adjust liquid sevoflurane infusion rate and as a way to predict the ET concentration within acceptable limits. As shown, the model’s predictive performance has a 3.9% average error in the 6-h analysis, this percentage being slightly higher for increases (5.0%) and decreases (5.5%) of target concentration. No significant differences are found in the MDAPE for the different sevoflurane target concentrations studied.

The model’s predictive performance is greater than other more complex predictive models of anesthetic uptake, which include changes in CO, temperature, etc., designed for liquid anesthetic bolus administration in closed system and for vaporizer adjustment during minimum flow anesthesia. The MDAPE values obtained with these models were 10.9% for sevoflurane,37 13%–17.2% for desflurane,30,32 and 18.7%–19.1% for enflurane.44 The best predictive values published are those obtained by the simpler model by Kennedy et al.30 and Heffernan et al.36 The constraints of the model have already been pointed out by Hendrickx et al.39 Despite the greater simplicity, the better predictive performance of our model may be partially due to its use with an open circuit, which means that all elements not related to uptake by the organs over time are excluded. Only losses through the ACD are to be added, and when the adjusted target concentration and minute ventilation are constant, losses are constant and equivalent to 50%–65% of the administered anesthetic. This fact can be the other main factor that minimizes the error of our model.

Likewise, predictive performance of the model (for any concentration and infusion time studied) is not only within acceptable limits for IV sedative and anesthetic infusion systems,45 but also below values reached in different studies29 using widely accepted clinical models.46,47 These large differences in the predictive performance of continuous IV infusion models among patients stem from the different evaluation methods29 and from inter-individual variations at physiological, genetic, or environmental levels, which have been analyzed by Gepts.46 Again, the better results obtained by our simpler model are explained basically by the high proportion of losses through the filter, which minimizes the error of the patient uptake model. The accurate calculation of these losses, which also includes conditioning factors (minute ventilation and ET sevoflurane), allows for reliable adjustment of the anesthetic administered.

On the other hand, the model demands hemodynamic stability, since the uptake is calculated based on the normal blood flow to the organs. In clinically unstable patients and/or while receiving other drugs such as narcotics, muscle relaxants, and benzodiazepines, a more frequent dose-titration may be needed. In this case a more frequent control of end-expiratory concentration of gas and monitoring of its sedative effects would be recommended. Obviously, the more complex models which consider the variation of CO, of ventilation/perfusion mismatch and other factors, could improve the performance of the system. However, increasing the complexity of a model does not always improve its predictive performance.44

A potential error source may be linked to the gas analyzer. The Vamos monitor’s accuracy is ±0.15% of the volume for sevoflurane, which is most acceptable for clinical use. However, because its display offers just one decimal, the minimum error calculated for each data-point is from 14% for a 0.7% ET sevoflurane to 6.6% for 1.5%. Using an agent monitor with finer resolution may have produced better results than those obtained. Another potential error source is the infusion syringe used. The volumetric accuracy of the Ivac P7000 is ±2%. In general terms, all syringes have similar accuracy and have been largely used in target-controlled infusion systems and for the injection of liquid anesthetics in a circle system,39 given their suitability for these types of applications. Other syringe types are not likely to improve the results. In our patients no problems in dosing associated with the pump, the syringe, or the infusion system were observed. However, at temperatures above 30°C both refill of the syringe and temporary removal of the filter can produce transient increases or decreases respectively in the ET concentration of anesthetic48,49 making the use of an anesthetic agent analyzer mandatory. Finally, although the predictive power of the algorithm is excellent, using caution to prevent errors in dosage is highly recommended. The anesthetic agent analyzer should be provided with alarms for a high-sevoflurane ET concentration, not just to detect predictable fluctuations from syringe refills, but also as a defense against human error and equipment failure. Ideally, this monitor should be programmed to automatically stop the infusion pump and sound an alarm. However, the standard of monitoring requirements when this device is used are yet to be described.

When drawing conclusions about the model, it is worth analyzing the clinical meaning of the results. The 3.9% mean PE (average of each patient’ medians, MDAPE) in the 6-h study shows that by adjusting the infusion rate to reach, for instance, a 1.5% target sevoflurane concentration, 50% of the obtained ET values will range between 1.44% and 1.56%. At the same time, the small negative bias means that in 95% of cases, ET sevoflurane values will be slightly below the target values. This is important for safety reasons, as overdosing is almost impossible and ET-concentration readjustments can be done by simply increasing the infusion rate following the increasing scheme which offers a similar predictive accuracy.

Another important feature is the fact that the infusion rate is readjusted once "induction time" has elapsed and is only changed once every hour. This makes bedside application easier, as one can make it coincide with hourly nursing evaluations in critical care patients. More hourly adjustments, as in circle system models of diverse complexity, e.g., seven liquid enflurane injections per hour,44 would not be clinically feasible in long ICU sedations. With the easy-to-handle model described, a computer-controlled system is no longer essential. A full chart of infusion regimes for patients of different weights and minute volumes is in Appendix 2 (available at www.anesthesia-analgesia.org).

Finally, the manufacturer’s recommendation for sevoflurane infusion may be useful to guide ACD use in clinical practice but many readjustments in infusion rate must be performed in order to avoid frequent PEs. The instructions for device use include a chart for calculating syringe pump rate to reach 0.5% gas concentration at different minute volumes. For 7.0 L/min, recommended rates are 3.0 and 2.2 mL/h for induction (30 min) and maintenance, respectively. Following our model, an initial pump rate of 3 mL/h for 30 min (induction) would produce an ET sevoflurane concentration of 0.54% (which would be displayed as 0.5% in a clinical gas-analyzer). The following reduction to 2.2 mL/h would produce a concentration of about 0.51% at the end of the first hour. This way PE for this period would be very good (<10%). However, from this initial period (1–2 h) the PE would increase progressively if the infusion rate were not reduced each hour in an exponential fashion (2.0-1.8-1.7- 1.6-1.5-1.4 ..... 1.1). That is to say, if 2.2 mL/h were maintained, the ET sevoflurane concentration would be close to 0.8% after 6 h of sedation and 1% at equilibrium (PE of 80%–100%). However, instructions for use of the ACD also stated that for changing the concentration, the relationship between concentration and syringe pump rate is nearly linear. This means that if a concentration of 1% were observed in the gas monitor, halving the infusion rate would reduce the concentration to half. If this rule was applied whenever the observed concentration shifted from the desired concentration, the infusion rate would be adjusted close to that obtained with our scheme.

In conclusion, this study documents the excellent predictive performance of a scheme for a manually adjusted, but pump-driven, infusion of liquid sevoflurane for use with the ACD in postoperative ICU patients with no respiratory pathologies. The predictive features help system safety and hourly adjustment facilitates its clinical use. The easy administration of inhaled sedation drugs in critical care using the ACD offers new approaches to sedation in the ICU,12 not only because of the better pharmacological features of inhaled drugs, but also because of the possibility of monitoring the concentration administered, a key safety aspect in continuous sedative administration. Used with accurate and simple infusion schemes, devices such as the ACD can improve sedation prospects in critical care patients.


   Appendix 2
Top
 Abstract
 Introduction
 METHODS
 RESULTS
 DISCUSSION
 Appendix 2
REFERENCES
 


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  		Table. Appendix 2. Chart of of Sevoflurane Infusion Regimes for Anaconda (ml/h) for Patients for Different Weights at Different Ventilatory Minute Volume Settings. Minute Volume (VE) is Calculated as 100 ml per Kg BW and 120% and +140% Considering a VT from 7–10 ml/kg and RF from 10–20 bpm

 


   Footnotes
 
This article has supplementary material on the Web site:www.anesthesia-analgesia.org.

Accepted for publication December 3, 2007.


   REFERENCES
Top
 Abstract
 Introduction
 METHODS
 RESULTS
 DISCUSSION
 Appendix 2
 REFERENCES
 

  1. Tung A, Rosenthal M. Patients requiring sedation. Crit Care Clin 1995;11:791–802[Web of Science][Medline]
  2. Durbin CG Jr. Sedation in the critically ill patient. New Horiz 1994;2:64–74[Medline]
  3. Jones C, Griffiths RD, Humphris G, Skirrow PM. Memory, delusions, and the development of acute posttraumatic stress disorder-related symptoms after intensive care. Crit Care Med 2001;29:573–80[Web of Science][Medline]
  4. Schnyder U, Morgeli H, Nigg C, Klaghofer R, Renner N, Trentz O, Buddeberg C. Early psychological reactions to life-threatening injuries. Crit Care Med 2000;28:86–92[Web of Science][Medline]
  5. Scragg P, Jones A, Fauvel N. Psychological problems following ICU treatment. Anaesthesia 2001;56:9–14[Web of Science][Medline]
  6. Schweickert WD, Gehlbach BK, Pohlman AS, Hall JB, Kress JP. Daily interruption of sedative infusions and complications of critical illness in mechanically ventilated patients. Crit Care Med 2004;32:1272–6[Web of Science][Medline]
  7. Ostermann ME, Keenan SP, Seiferling RA, Sibbald WJ. Sedation in the intensive care unit: a systematic review. JAMA 2000;283:1451–9[Abstract/Free Full Text]
  8. Mendel PR, White PF. Sedation of the critically ill patient. Int Anesthesiol Clin 1993;31:185–200[Web of Science][Medline]
  9. Kress JP, O’Connor MF, Pohlman AS, Hall JB. Propofol versus midazolam in critically ill patients. Crit Care Med 1997;25:554–5[Web of Science][Medline]
  10. Izurieta R, Rabatin JT. Sedation during mechanical ventilation: a systematic review. Crit Care Med 2002;30:2644–8[Web of Science][Medline]
  11. Crippen DW. The role of sedation in the ICU patient with pain and agitation. Crit Care Clin 1990;6:369–92[Web of Science][Medline]
  12. Kong KL, Bion JF. Sedating patients undergoing mechanical ventilation in the intensive care unit. Winds of change? Br J Anaesth 2003;90:267–9[Free Full Text]
  13. Jacobi J, Fraser GL, Coursin DB, Riker RR, Fontaine D, Wittbrodt ET, Chalfin DB, Masica MF, Bjerke HS, Coplin WM, Crippen DW, Fuchs BD, Kelleher RM, Marik PE, Nasraway SA Jr, Murray MJ, Peruzzi WT, Lumb PD. Task Force of the Am College of Critical Care Med (ACCM) of the Society of Critical Care Med (SCCM), Am Society of Health-System Pharmacists (ASHP), Am College of Chest Physicians. Clinical practice guidelines for the sustained use of sedatives and analgesics in the critically ill adult. Crit Care Med 2002;30:119–41[Web of Science][Medline]
  14. Millane TA, Bennett ED, Grounds RM. Isoflurane and propofol for long-term sedation in the intensive care unit. A crossover study. Anaesthesia 1992;47:768–74[Web of Science][Medline]
  15. Kong KL, Willatts SM, Prys-Roberts C. Isoflurane compared with midazolam for sedation in the intensive care unit. BMJ 1989;298:1277–80[Abstract/Free Full Text]
  16. Spencer EM, Willatts SM. Isoflurane for prolonged sedation in the intensive care unit; efficacy and safety. Intensive Care Med 1992;18:415–21[Web of Science][Medline]
  17. Halpenny D. Sevoflurane sedation. Can J Anaesth 2000;47:193–4[Web of Science][Medline]
  18. Ibrahim AE, Ghoneim MM, Kharasch ED, Epstein RH, Groudine SB, Ebert TJ, Binstock WB, Philip BK. Sevoflurane Sedation Study Group. Speed of recovery and side-effect profile of sevoflurane sedation compared with midazolam. Anesthesiology 2001;94:87–94[Web of Science][Medline]
  19. Meiser A, Sirtl C, Bellgardt M, Lohmann S, Garthoff A, Kaiser J, Hugler P, Laubenthal HJ. Desflurane compared with propofol for postoperative sedation in the intensive care unit. Br J Anaesth 2003;90:273–80[Abstract/Free Full Text]
  20. Meiser A, Laubenthal H. Inhalational anaesthetics in the ICU: theory and practice of inhalational sedation in the ICU, economics, risk-benefit. Best Pract Res Clin Anaesthesiol 2005;19:523–38[Medline]
  21. De Hert SG, Van der Linden PJ, Cromheecke S, Meeus R, Nelis A, Van Reeth V, ten Broecke PW, De Blier IG, Stockman BA, Rodrigus IE. Cardioprotective properties of sevoflurane in patients undergoing coronary surgery with cardiopulmonary bypass are related to the modalities of its administration. Anesthesiology 2004;101:299–310[Web of Science][Medline]
  22. De Hert SG, Van der Linden PJ, Cromheecke S, Meeus R, ten Broecke PW, De Blier IG, Stockman BA, Rodrigus IE. Choice of primary anesthetic regimen can influence intensive care unit length of stay after coronary surgery with cardiopulmonary bypass. Anesthesiology 2004;101:9–20[Web of Science][Medline]
  23. Ghatge S, Lee J, Smith I. Sevoflurane: an ideal agent for adult day-case anesthesia? Acta Anaesthesiol Scand 2003;47:917–31[Web of Science][Medline]
  24. Enlund M, Wiklund L, Lambert H. A new device to reduce the consumption of a halogenated anesthetic agent. Anaesthesia 2001;56:429–32[Web of Science][Medline]
  25. Enlund M, Lambert H, Wiklund L. The sevoflurane saving capacity of a new anesthetic agent conserving device compared with a low flow circle system. Acta Anaesthesiol Scand 2002;46:506–11[Web of Science][Medline]
  26. Tempia A, Olivei MC, Calza E, Lambert H, Scotti L, Orlando E, Livigni S, Guglielmotti E. The anaesthetic conserving device compared with conventional circle system used under different flow conditions for inhaled anesthesia. Anesth Analg 2003;96:1056–61[Abstract/Free Full Text]
  27. Sackey PV, Martling CR, Granath F, Radell PJ. Prolonged isoflurane sedation of intensive care unit patients with the anesthetic conserving device. Crit Care Med 2004;32:2241–6[Web of Science][Medline]
  28. Varvel JR, Donoho DL, Shafer SL. Measuring the predictive performance of computer-controlled infusion pumps. J Pharmacokinet Biopharm 1992;20:63–94[Web of Science][Medline]
  29. Veselis RA, Glass P, Dnistrian A, Reinsel R. Performance of computer-assisted continuous infusion at low concentrations of intravenous sedatives. Anesth Analg 1997;84:1049–57[Abstract]
  30. Kennedy RR, French RA, Spencer C. Predictive accuracy of a model of volatile anesthetic uptake. Anesth Analg 2002;95:1616–21[Abstract/Free Full Text]
  31. Lerou JG, Booij LH. Model-based administration of inhalation anaesthesia. 1. Developing a system model. Br J Anaesth 2001;86:12–28[Abstract/Free Full Text]
  32. Lerou JG, Booij LH. Model-based administration of inhalation anaesthesia. 2. Exploring the system model. Br J Anaesth 2001;86:29–37[Abstract/Free Full Text]
  33. Mondello E, Siliotti R, Noto G, Cuzzocrea E, Scollo G, Trimarchi G, Venuti FS. Bispectral Index in ICU: correlation with Ramsay Score on assessment of sedation level. J Clin Monit Comput 2002;17:271–7[Medline]
  34. Lowe HJ. The quantitative practice of anesthesia. Baltimore: Williams and Wilkins, 1981
  35. Heffernan PB, Gibbs JM, McKinnon AE. Teaching the uptake and distribution of halothane. A computer simulation program. Anaesthesia 1982;37:9–17[Web of Science][Medline]
  36. Heffernan PB, Gibbs JM, McKinnon AE. Evaluation of a computer simulation program for teaching halothane uptake and distribution. Anaesthesia 1982;37:43–6[Web of Science][Medline]
  37. Kennedy RR, Baker AB. The effect of cardiac output changes on end-expired volatile anesthetic concentrations. A theoretical study. Anaesthesia 2001;56:1034–40[Web of Science][Medline]
  38. Weir HM, Kennedy RR. Infusing liquid anaesthetics into a closed circuit. Anaesth Intensive Care 1994;22:376–9[Web of Science][Medline]
  39. Hendrickx JF, Van Zundert AA, De Wolf AM. Sevoflurane pharmacokinetics: effect of cardiac output. Br J Anaesth 1998;81:495–501[Abstract/Free Full Text]
  40. Boller M, Moens Y, Kästner SB, Bettschart-Wolfensberger R. Closed system anaesthesia in dogs using liquid sevoflurane injection; evaluation of the square-root-of-time model and the influence of CO2 absorbent. Vet Anesthe Analg 2005;32:168–77
  41. Loockwood GC, Chakrabarti MK, Whitwam JG. A computer-controlled closed anaesthetic breathing system. Anaesthesia 1993;48:690–3[Web of Science][Medline]
  42. Hans P, Coussaert E, Cantraine F, Pieron F, Dewandre PY, d’Hollander A, Lamy M. Predictive accuracy of continuous propofol infusions in neurosurgical patients: comparison of pharmacokinetic models. J Neurosurg Anesthesiol 1997;9:112–17[Web of Science][Medline]
  43. Shibutani K, Inchiosa MA Jr, Sawada K, Bairamian M. Accuracy of pharmacokinetic models for predicting plasma fentanyl concentrations in lean and obeses surgical patients: derivation of dosing weight ("pharmacokinetic mass"). Anesthesiology 2004;101:603–13[Web of Science][Medline]
  44. Vermeulen PM, Kalkman CJ, Dirksen R, Knape JT, Moons KG, Borm GF. Predictive performance of a physiological model for enflurane closed-circuit anaesthesia: effects of continuous cardiac output measurements and age-related solubility data. Br J Anaesth 2002;88:38–45[Abstract/Free Full Text]
  45. Swinhoe CF, Peacock JE, Glen JB, Reilly CS. Evaluation of the predictive performance of a ‘Diprifusor’ TCI system. Anaesthesia 1998;53(suppl 1):61–7[Web of Science][Medline]
  46. Gepts E. Pharmacokinetic concepts for TCI anaesthesia. Anaesthesia 1998;53(suppl 1):4–12[Web of Science][Medline]
  47. Marsh B, White M, Morton N, Kenny GN. Pharmacokinetic model driven infusion of propofol in children. Br J Anaesth 1991;67:41–8[Abstract/Free Full Text]
  48. Berton J, Sargentini C, Nguyen JL, Belii A, Beydon L. AnaConDaTM reflection filter: Bench and patient evaluation of safety and volatile anesthetic conservation. Anesth Analg 2006;104: 130–4[Web of Science]
  49. Henning JDR, Bateman R. Excess delivery of isoflurane liquid from a syringe driver. Anaesthesia 2004;59:1251[Medline]
  50. Malviya S, Lerman J. The blood/gas solubilities of sevoflurane, isoflurane, halothane, and serum constituent concentrations in neonates and adults. Anesthesiology 1990;72:793–6[Web of Science][Medline]
  51. Lerou JG, Booij LH. Model-based administration of inhalation anaesthesia. 3. Validating the system model. Br J Anaesth 2002;88:24–37[Abstract/Free Full Text]
  52. Mapleson WW. Circulation-time models of the uptake of inhaled anesthetics and data for quantifying them. Br J Anaesth 1973;45:319–34[Abstract/Free Full Text]
  53. Davis NR, Mapleson WW. Structure and quantification of a physiological model of the distribution of injected agents and inhaled anesthetics. Br J Anaesth 1981;53:399–405[Abstract/Free Full Text]
  54. Yasuda N, Lockhart S, Eger EI II, Weiskopf RB, Liu J, Laster M, Taheri S, Peterson NA. Comparison of kinetics of sevoflurane and isoflurane in humans. Anesth Analg 1991;72:316–24[Abstract/Free Full Text]



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