Target Controlled Infusion Model Research Articles

Mimicking the Eleveld propofol target-controlled infusion model using the Marsh model with weight adjustment in a super-obese patient

Mimicking the Eleveld propofol target-controlled infusion model using the Marsh model with weight adjustment in a super-obese patient

General purpose propofol target-controlled infusion using the marsh model with adjusted weight input.

We report a simple method for adjusting the weight input of the Marsh target-controlled infusion (TCI) model such that the resulting infusion regime closely mimics the behaviour of the Eleveld model, thereby making the Marsh model more precise for patients at the extremes of age and body mass index. To assess the performance of our method, we simulated 2768 subjects with diverse combinations of age, weight, height and sex undergoing a hypothetical four-hour propofol TCI using both the Marsh model with our weight adjustment and the Eleveld model. The weight adjusted Marsh model produced infusion regimes and corresponding effect site concentrations closely mimicking that of the Eleveld model at all time points, with median and maximum absolute performance errors less than 8.1% and 20.3%, respectively, across the entire cohort. Our weight adjustment method is a simple and robust way of improving the precision of the Marsh model in patients at extremes of age and body mass index, until general purpose TCI models for propofol, such as the Eleveld model, become more widely available in commercial infusion pumps.

Target-controlled infusion - Past, present, and future.

Target-controlled infusion (TCI) is a novel drug delivery system wherein a microprocessor calculates the rate of drug to be infused based upon the target plasma or effect site concentration set by the operator. It has found its place in the operation theaters and intensive care units (ICUs) for safe administration of intravenous anesthesia and analgosedation using drugs like propofol, dexmedetomidine, opioids, and so on. Operating a TCI device requires the user to have a primitive understanding of drug pharmacokinetics and pharmacodynamics and an awareness of the practical problems that can arise during its administration. Ongoing research supports their usage in other clinical settings and for various other drugs such as antibiotics, vasopressors, and so on. In this article, we review the underlying principles and commonly used drugs for TCI, the practical aspects of its implementation, and the scope of this technology in future. TCI technology is increasingly being used in the field of anesthesiology and critical care due to the myriad advantages it offers when compared to manual infusions. It is, therefore, essential for the reader to understand the relevant principles and practical aspects related to TCI technology, as well as to be aware of the commonly used TCI models.

Comparison of Dexmedetomidine Versus Fentanyl-Based Anesthetic Protocols Under Patient State Index Guidance in Patients Undergoing Elective Neurosurgical Procedures with Intraoperative Neurophysiological Monitoring.

Objectives The study was designed to elucidate the effects of dexmedetomidine as an anesthetic adjunct to propofol in total intravenous anesthesia (TIVA) on anesthetic dose reduction, the quality of intraoperative neurophysiological monitoring (IONM) recordings, analgesic requirements, and recovery parameters in patients undergoing neurosurgical procedures with neurophysiological monitoring. Methods A total of 54 patients for elective neurosurgical procedures with IONM were randomized to group D (dexmedetomidine) and group F (fentanyl). A loading dose of the study drug of 1µg/kg followed by 0.5 µg/kg/h infusion was used in two groups. Propofol-based TIVA with a Schneider target-controlled infusion model was used for induction and maintenance with effect site concentration of 4-5 and 2.5-4 µg/mL, respectively, titrated to a Patient State Index (PSI) of 25-40. Baseline IONM recordings were obtained after induction. The mean propofol consumption, number of patient movements, quality of IONM recordings, number of fentanyl boluses, hemodynamic characteristics, and recovery parameters were recorded. Results The mean propofol consumption was significantly lower in group D when compared to group F (101.4 ± 13.5 µg/kg/min vs 148.0 ± 29.8 µg/kg/min). Baseline IONM recordings were acquired in all patients without any difficulty. The two groups were comparable with respect to the number of additional boluses of fentanyl, patient movements, and recovery characteristics. Conclusion Dexmedetomidine as an adjuvant to propofol in TIVA reduces the requirement of the latter, without affecting the IONM recordings. The addition of dexmedetomidine also ensures stable hemodynamics and decreases the requirement of opioids with similar recovery characteristics.

A Review of Current Literature of Interest to the Office-Based Anesthesiologist.

A Review of Current Literature of Interest to the Office-Based Anesthesiologist.

General Purpose Pharmacokinetic-Pharmacodynamic Models for Target-Controlled Infusion of Anaesthetic Drugs: A Narrative Review.

Target controlled infusion (TCI) is a clinically-available and widely-used computer-controlled method of drug administration, adjusting the drug titration towards user selected plasma- or effect-site concentrations, calculated according to pharmacokinetic-pharmacodynamic (PKPD) models. Although this technology is clinically available for several anaesthetic drugs, the contemporary commercialised PKPD models suffer from multiple limitations. First, PKPD models for anaesthetic drugs are developed using deliberately selected patient populations, often excluding the more challenging populations, such as children, obese or elderly patients, of whom the body composition or elimination mechanisms may be structurally different compared to the lean adult patient population. Separate PKPD models have been developed for some of these subcategories, but the availability of multiple PKPD models for a single drug increases the risk for invalid model selection by the user. Second, some models are restricted to the prediction of plasma-concentration without enabling effect-site controlled TCI or they identify the effect-site equilibration rate constant using methods other than PKPD modelling. Advances in computing and the emergence of globally collected databases has allowed the development of new “general purpose” PKPD models. These take on the challenging task of identifying the relationships between patient covariates (age, weight, sex, etc) and the volumes and clearances of multi-compartmental pharmacokinetic models applicable across broad populations from neonates to the elderly, from the underweight to the obese. These models address the issues of allometric scaling of body weight and size, body composition, sex differences, changes with advanced age, and for young children, changes with maturation and growth. General purpose models for propofol, remifentanil and dexmedetomidine have appeared and these greatly reduce the risk of invalid model selection. In this narrative review, we discuss the development, characteristics and validation of several described general purpose PKPD models for anaesthetic drugs.

Online exhaled propofol monitoring in normal-weight and obese surgical patients.

BackgroundIon mobility spectrometry (IMS) allows for online quantification of exhaled propofol concentrations. We aimed to validate a bedside online IMS device, the Edmon®, for predicting plasma concentrations of propofol in normal‐weight and obese patients.MethodsPatients with body mass index (BMI) >20 kg/m2 scheduled for laparoscopic cholecystectomy or bariatric surgery were recruited. Exhaled propofol concentrations (CA), arterial plasma propofol concentrations (CP) and bispectral index (BIS) values were collected during target‐controlled infusion (TCI) anaesthesia. Generalised estimation equation (GEE) was applied to all samples and stable‐phase samples at different delays for best fit between CP and CA. BMI was evaluated as covariate. BIS and exhaled propofol correlations were also assessed with GEE.ResultsA total of 29 patients (BMI 20.3–53.7) were included. A maximal R 2 of 0.58 was found during stable concentrations with 5 min delay of CA to CP; the intercept a = −0.69 (95% CI −1.7, 0.3) and slope b = 0.87 (95% CI 0.7, 1.1). BMI was found to be a non‐significant covariate. The median absolute performance error predicting plasma propofol concentrations was 13.4%. At a CA of 5 ppb, the model predicts a CP of 3.6 μg/ml (95% CI ±1.4). There was a maximal negative correlation of R 2 = 0.44 at 2‐min delay from CA to BIS.ConclusionsOnline monitoring of exhaled propofol concentrations is clinically feasible in normal‐weight and obese patients. With a 5‐min delay, our model outperforms the Marsh plasma TCI model in a post hoc analysis. Modest correlation with plasma concentrations makes the clinical usefulness questionable.

Obesity and anesthetic pharmacology: simulation of target-controlled infusion models of propofol and remifentanil.

The prevalence of obesity is increasing, resulting in an increase in the number of surgeries performed to treat obesity and diseases induced by obesity. The associated comorbidities as well as the pharmacokinetic and pharmacodynamic changes that occur in obese patients make it difficult to control the appropriate dose of anesthetic agents. Factors that affect pharmacokinetic changes include the increase in adipose tissue, lean body weight, extracellular fluid, and cardiac output associated with obesity. These physiological and body compositional changes cause changes in the pharmacokinetic and pharmacodynamic parameters. The increased central volume of distribution and alterations in the clearance of drugs affect the plasma concentration of propofol and remifentanil in the obese population. Additionally, obesity can affect pharmacodynamic properties, such as the 50% of maximal effective concentration and the effect-site equilibration rate constant (ke0). Conducting a simulation of target-controlled infusions based on pharmacokinetic and pharmacodynamic models that include patients that are obese can help clinicians better understand the pharmacokinetic and pharmacodynamic changes of anesthetic drugs associated with this population.

Relationship Between Propofol Target Concentrations, Bispectral Index, and Patient Covariates During Anesthesia.

Internationally, propofol is commonly titrated by target-controlled infusion (TCI) to maintain a processed electroencephalographic (EEG) parameter (eg, bispectral index [BIS]) within a specified range. The overall variability in propofol target effect-site concentrations (CeT) necessary to maintain adequate anesthesia in real-world conditions is poorly characterized, as are the patient demographic factors that contribute to this variability. This study explored these issues, hypothesizing that the variability in covariate-adjusted propofol target concentrations during BIS-controlled anesthesia would be substantial and that most of the remaining interpatient variability in drug response would be due to random effects, thus suggesting that the opportunity to improve on the Schnider model with further demographic data is limited. With ethics committee approval and a waiver of informed consent, a deidentified, high-resolution, intraoperative database consisting of propofol target concentrations, BIS values, and vital signs from 13,239 patients was mined to identify patients who underwent general endotracheal anesthesia using propofol (titrated to BIS), fentanyl, remifentanil, and rocuronium that lasted at least 1 hour. The propofol target concentrations and BIS values 30 minutes after incision (CeT30 and BIS30) were considered representative of stable intraoperative conditions. The data were plotted and analyzed by descriptive statistics. Confidence intervals were computed using a bootstrap method. A linear model was fit to the data to test for correlation with factors of interest (eg, age and weight). A total of 4584 patients met inclusion criteria and were entered into the analysis. Of the propofol target concentrations, 95% were between 1.5 and 3.5 µg·mL-1. Higher BIS30 values were correlated with higher propofol concentrations. Except for age, all the patient-related variables analyzed entered the regression model linearly. Only 10.2% of the variability in CeT30 was explained by the patient factors of age and weight combined. Our hypothesis was confirmed. The variability in covariate-adjusted propofol CeT30 titrated to BIS in real-world conditions is considerable, and only a small portion of the remaining variability in drug response is explained by patient demographic factors. This finding may have important implications for the development of new pharmacokinetic (PK) models for propofol TCI.

A pharmacokinetic model optimized by covariates for propofol target-controlled infusion in dogs

ObjectiveTo develop a population pharmacokinetic model for propofol target-controlled infusion (TCI) in dogs and to evaluate its performance for use in the clinical setting. Study designProspective clinical study. AnimalsA group of 40 client-owned dogs undergoing general anaesthesia for magnetic resonance imaging. MethodsPropofol was administered to 26 premedicated dogs and arterial blood samples were collected during the infusion and over 240 minutes after terminating the infusion. Propofol concentrations were measured by high-performance liquid chromatography. A population pharmacokinetic analysis was performed using a nonlinear mixed-effects modelling approach, allowing inter- and intra-individual variability estimation and quantitative evaluation of the influence of the following covariates: weight, body condition score, age, size-related age (Age_size), sex, premedication type, size and contrast agent administration. A final model was obtained using a stepwise approach in which individual covariate effects on each pharmacokinetic variable were incorporated. The performance of the developed TCI model was subsequently evaluated while inducing and maintaining anaesthesia in 14 premedicated dogs and assessed by comparing predicted and measured concentrations at specific time points. ResultsPropofol pharmacokinetics was best described by a three-compartment model. Weight, Age_size, premedication and sex showed significant pharmacokinetic effects. Addition of the significant covariate/variable associations to the final model resulted in a reduction of the objective function value from 285.53 to –22.34. The median values of prediction error and absolute performance error were 3.1% and 28.4%, respectively. Induction targets between 4.0 and 6.5 μg mL–1 allowed intubation within 5.0 ± 0.9 minutes. Anaesthesia was achieved with targets between 3.0 and 6.5 μg mL–1. Mean time to extubation was 9.7 ± 2.6 minutes. All dogs recovered smoothly and without complications. Conclusions and clinical relevanceOverall predictive performance of the pharmacokinetic model-driven infusion developed was clinically acceptable for administering propofol to dogs in routine anaesthesia.

Pharmacokinetic Analysis of Propofol Target-Controlled Infusion Models in Chinese Patients with Hepatic Insufficiency.

BackgroundEffects of liver dysfunction on target-controlled infusion (TCI) with Marsh parameters of propofol remain poorly documented. The purpose of this study was to evaluate the performance of propofol TCI in a cohort of Chinese patients with severe hepatic insufficiency.Material/MethodsWe assigned 32 patients who underwent liver transplantation to 3 groups according to Child-Turcotte-Pugh (CTP) score. Anesthesia, preceding liver transplantation, was induced and maintained with TCI of 3 μg/mL propofol. Plasma propofol concentration was assessed. Propofol TCI system performance was analyzed in terms of error size, bias, and divergence. Data on plasma propofol concentrations were analyzed, and population pharmacokinetic parameters of propofol were fitted by NONMEM software.ResultsIn the CTP C group, measured concentrations of propofol were much higher than those of predictive concentrations, with significantly higher overshoots compared to CTP A patients. Overall, TCI system performance was significantly lower in CTP C patients. Linear regression equations of Cm vs. Cp and a regression model of pharmacokinetics were obtained.ConclusionsPropofol TCI device performance with Marsh parameters was clinically acceptable in CTP A patients but may not be suitable for patients with severe hepatic impairment.

Principles of total intravenous anaesthesia: practical aspects of using total intravenous anaesthesia

### Key points Advanced pharmacokinetic models for target-controlled infusion (TCI) have facilitated an increasing use of total i.v. anaesthesia (TIVA) in various clinical settings. The technical complexity and labour-intensive methodology of TIVA can deter clinicians and lead to default use of a volatile agent. In theory, any combination of i.v. hypnotic(s) and opioid(s) can be used and opioid-free techniques are described. In practice, the synergy between TCI infusions of propofol and remifentanil proves highly effective at obtunding response to noxious stimuli1 and for this article constitutes ‘ideal’ TIVA. This drug combination achieves equilibrium between adequate depth of anaesthesia and rapid recovery. Intermittent boluses of agents or manually controlled infusions may produce an inadequate effect.2 The specific indications for TIVA are given in Table 1. TIVA is applicable to nearly all types of surgery but has particular value in clinical scenarios where a stress-free awake extubation free of laryngospasm is required. TIVA confers many advantages over a conventional volatile technique, particularly a better recovery profile with reduced risk of postoperative nausea and vomiting, and can facilitate intraoperative wake-up while retaining amnesia. The use of TIVA for cases requiring a rapid intubation sequence is controversial but is safely practiced. View this table: Table 1 Specific indications for …

Propofol target-controlled infusion modeling in rabbits: Pharmacokinetic and pharmacodynamic analysis.

This study aimed to establish a new propofol target-controlled infusion (TCI) model in animals so as to study the general anesthetic mechanism at multi-levels in vivo. Twenty Japanese white rabbits were enrolled and propofol (10 mg/kg) was administrated intravenously. Artery blood samples were collected at various time points after injection, and plasma concentrations of propofol were measured. Pharmacokinetic modeling was performed using WinNonlin software. Propofol TCI within the acquired parameters integrated was conducted to achieve different anesthetic depths in rabbits, monitored by narcotrend. The pharmacodynamics was analyzed using a sigmoidal inhibitory maximal effect model for narcotrend index (NI) versus effect-site concentration. The results showed the pharmacokinetics of propofol in Japanese white rabbits was best described by a two-compartment model. The target plasma concentrations of propofol required at light anesthetic depth was 9.77±0.23 μg/mL, while 12.52±0.69 μg/mL at deep anesthetic depth. NI was 76.17±4.25 at light anesthetic depth, while 27.41±5.77 at deep anesthetic depth. The effect-site elimination rate constant (ke0) was 0.263/min, and the propofol dose required to achieve a 50% decrease in the NI value from baseline was 11.19 μg/mL (95% CI, 10.25-13.67). Our results established a new propofol TCI animal model and proved the model controlled the anesthetic depth accurately and stably in rabbits. The study provides a powerful method for exploring general anesthetic mechanisms at different anesthetic depths in vivo.

Measured versus predicted blood propofol concentrations in children during scoliosis surgery.

Propofol anesthesia is preferred during scoliosis surgery because it suppresses evoked potential spinal cord function less than other drugs and better enables the detection of spinal cord ischemia. In this study, we determined the difference between the true and predicted blood propofol levels during target-controlled infusions in children during scoliosis surgery. Arterial blood propofol measured concentrations (Cm) were compared with predicted concentrations (Cp) approximately every 30 minutes during the maintenance phase of anesthesia in 20 children. Whole blood propofol concentrations were measured using a point-of-care blood propofol analyzer. Anesthesia management was not affected by the study. The median performance error, median absolute performance error, wobble, and divergence were calculated. Children were aged 9 to 17 years and weighed 26.5 to 95 kg. The Paedfusor model was used in 16 children and the Marsh model in 4 children. In 154 blood propofol measurements, the mean difference between the Cm and Cp was 1.5 µg·mL (limits of agreement, -1.4 to 4.5 µg·mL), and the mean performance error was 44.7% (limits of agreement, -40.1% to 130.2%). The median performance error and median absolute performance error for the whole group were 39.8% (range, -20.9% to 103.3%) and 39.8% (range, 20%-103.3%), respectively. The performance errors improved with increase in duration of infusion (divergence, -2.2 [range, -1.03 to 0.13]). Cm was almost always larger than Cp except in 2 children who had consistently lower Cm than Cp (lowest Cm(s) were 1.74 and 1.96 µg·mL when the Cp was 3 µg·mL); both had the Paedfusor model and their body weights were 28 and 33 kg. Propofol target-controlled infusion models had poor performance characteristics in children undergoing scoliosis surgery. Point-of-care propofol assay may enable adjustment of the infusion to better achieve the intended blood level.

Performance of propofol target-controlled infusion models in the obese: pharmacokinetic and pharmacodynamic analysis.

Obesity is associated with important physiologic changes that can potentially affect the pharmacokinetic (PK) and pharmacodynamic (PD) profile of anesthetic drugs. We designed this study to assess the predictive performance of 5 currently available propofol PK models in morbidly obese patients and to characterize the Bispectral Index (BIS) response in this population. Twenty obese patients (body mass index >35 kg/m), aged 20 to 60 years, scheduled for laparoscopic bariatric surgery, were studied. Anesthesia was administered using propofol by target-controlled infusion and remifentanil by manually controlled infusion. BIS data and propofol infusion schemes were recorded. Arterial blood samples to measure propofol were collected during induction, maintenance, and the first 2 postoperative hours. Median performance errors (MDPEs) and median absolute performance errors (MDAPEs) were calculated to measure model performance. A PKPD model was developed using NONMEM to characterize the propofol concentration-BIS dynamic relationship in the presence of remifentanil. We studied 20 obese adults (mean weight: 106 kg, range: 85-141 kg; mean age: 33.7 years, range: 21-53 years; mean body mass index: 41.4 kg/m, range: 35-52 kg/m). We obtained 294 arterial samples and analyzed 1431 measured BIS values. When total body weight (TBW) was used as input of patient weight, the Eleveld allometric model showed the best (P < 0.0001) performance with MDPE = 18.2% and MDAPE = 27.5%. The 5 tested PK models, however, showed a tendency to underestimate propofol concentrations. The use of an adjusted body weight with the Schnider and Marsh models improved the performance of both models achieving the lowest predictive errors (MDPE = <10% and MDAPE = <25%; all P < 0.0001). A 3-compartment PK model linked to a sigmoidal inhibitory Emax PD model by a first-order rate constant (ke0) adequately described the propofol concentration-BIS data. A lag time parameter of 0.44 minutes (SE = 0.04 minutes) to account for the delay in BIS response improved the fit. A simulated effect-site target of 3.2 μg/mL (SE = 0.17 μg/mL) was estimated to obtain BIS of 50, in the presence of remifentanil, for a typical patient in our study. The Eleveld allometric PK model proved to be superior to all other tested models using TBW. All models, however, showed a trend to underestimate propofol concentrations. The use of adjusted body weight instead of TBW with the traditional Schnider and Marsh models markedly improved their performance achieving the lowest predictive errors of all tested models. Our results suggest no relevant effect of obesity on both the time profile of BIS response and the propofol concentration-BIS relationship.

Anesthetic management of a preterm neonate intracranial aneurysm clipping.

Anesthetic management of a preterm neonate intracranial aneurysm clipping.

Changes in total and unbound concentrations of sufentanil during target controlled infusion for cardiac surgery with cardiopulmonary bypass

Target controlled infusion (TCI) with sufentanil is usually performed using the Gepts model, which was derived from patients undergoing general surgery. It is, however, known that pharmacokinetics of sufentanil can be changed during cardiopulmonary bypass (CPB). We tested whether TCI during coronary artery bypass surgery with CPB produces constant total, unbound sufentanil concentration-time course or both. After IRB approval, written informed consent was obtained from 38 male patients (48-74 yr) undergoing coronary artery bypass surgery. Anaesthesia was managed with propofol and TCI of sufentanil, using the Gepts model, targeting plasma concentrations of 0.4 (n=18) or 0.8 ng ml(-1) (n=20). Arterial blood samples were taken before, during, and after CPB. Total and unbound sufentanil concentrations were measured by HPLC with tandem mass spectrometry. The accuracy of the TCI model was assessed by the prediction error, and a pharmacokinetic model was determined by population analysis. The median prediction error of the TCI with the Gepts model before, during, and after CPB was 59.6, 3.9, and -10.4%, respectively. The unbound sufentanil concentrations increased significantly during CPB. Pharmacokinetic modelling showed an increase in elimination and intercompartmental clearance after initiation of CPB. Neither total nor unbound sufentanil concentrations remained constant when performing a TCI with the Gepts model in coronary artery bypass surgery with CPB. A pharmacokinetic model derived from patients undergoing cardiac surgery with CPB might improve the performance of TCI in this population.

Analysis of total and unbound hydromorphone in human plasma by ultrafiltration and LC–MS/MS: Application to clinical trial in patients undergoing open heart surgery

A method for a sensitive and specific analysis of hydromorphone total and unbound drug concentrations in human plasma was developed and validated. Sample preparation was preceded with an ultrafiltration step to separate the unbound drug from the protein bound fraction of hydromorphone. Both the ultrafiltrate and plasma samples were extracted with solid-phase extraction and substituted with stable isotope-labeled hydromorphone that was used as internal standard. Chromatographic separation was performed by gradient elution with UPLC-like system and eluates were analyzed by tandem mass spectrometry equipped with an electrospray ionization source. Sample preparation was optimized for good recovery of hydromorphone and the results were consistent. Calibration curves demonstrated linearity in the concentration range of 78-5000pg/ml for analysis of both total and unbound concentrations of hydromorphone. The limit of detection was 1pg and the lower limit of quantification was 78pg/ml for both total and unbound hydromorphone plasma drug concentrations. Intra- and interassay reproducibility and inaccuracy did not exceed 10%. Hydromorphone was on the average 14% bound to plasma proteins, supporting the previously published unreferenced statements that the protein binding of hydromorphone is low. Method was applied to a clinical trial in patients undergoing open heart surgery to generate a target controlled infusion model for the postoperative patient controlled analgesia with hydromorphone.

Presenting Data versus Predictions as Basic Scientific Information: Target-controlled Infusions versus Microgram per Kilogram per Minutes

Cleveland Clinic, Cleveland, Ohio. kempenp@ccf.orgIn the August issue of Anesthesiology, I found two articles of particular interest regarding propofol administration.1,2I was simply confounded by the fact that target-controlled infusion (TCI) “predicted” concentrations have become the basic jargon for scientific papers. In both articles, I never found any TRUE raw data disclosing the actual dose of drug administered to these patients. In addition, the index of anesthesia in the article by Rigouzzo et al. 2was the bispectral index value (another proprietary, i.e. , undisclosed program). In particular, the article by Rigouzzo et al. 2demonstrated that true differences exist between the multiple studied TCI models (and probably all others as well). I was confounded for several reasons: (1) TCI is not currently used in the United States and probably will remain withheld from clinical use by the Food and Drug Administration; (2) there apparently are multiple TCI devices with unknown (to any U.S. clinician) validity and deviations in ability/accuracy; and (3) TCI values are predictions and not measured values in any individual study; (4) multiple variables influence actual plasma concentrations in any given patient or patient group; and (5) finally, the actual TCI infusion rates change over time. Our journal (Anesthesiology) is a publication of the American Society of Anesthesiologists, where practice remains relevant in terms of microgram per kilogram per minute during propofol infusion. It would seem appropriate to require, at a bare minimum, presentation of this pertinent information to the readership (at least alongside TCI values) for several reasons: (1) microgram per kilogram per minute is the American “frame of reference”; (2) microgram per kilogram per minute is REAL and not proposed/extrapolated scientific information; and (3) TCI devices should/must disclose the instantaneous infusion rate during the relevant study periods.Although I understand the practicability of “indexing anesthetic depth” to some form of electroencephalogram monitor for studies for total intravenous anesthesia anesthetics, I would hope the Journal would also require end-tidal gas concentration disclosure for any inhaled agent mentioned in a manuscript. As a clinical scientist, it is essential to know what is actually being administered to correlate to truly dependent variables such as bispectral index or TCI, especially because no single electroencephalogram monitor or TCI program has been accepted as the standard for scientific studies or even clinical use in the United States. I concluded that I simply came away from both articles without meaningful clinical information—clinical information being why I read this journal. I personally suspect Bandschapp et al. 1found “analgesic properties of propofol” simply because pain is the conscious perception of noxious stimulation, and impairment of consciousness resulted in these findings (with probably 60 microgram per kilogram per minute of propofol infusing). Perhaps Anesthesiology might lead the world's journals to take on such a basic standard of presenting facts (infusion rates) instead of predictions (TCI/bispectral index) as basic science and in the interests of our readership.Cleveland Clinic, Cleveland, Ohio. kempenp@ccf.org

ZURÜCKGEZOGEN: Propofolapplikationssysteme

During anaesthesia propofol is administered either by manual controlled infusion (MCI) or by target controlled infusion (TCI) techniques. In this study two different TCI systems for propofol administration were evaluated with regard to handling, patient safety, and costs and compared to administration of propofol by the MCI technique. In a prospective study, 90 patients scheduled for elective surgery of the nose or nasal sinuses were randomly enrolled in three groups. The two TCI systems were examined in two groups of 30 patients: one group received propofol following the pharmacokinetic TCI model of Schnider (TCI-Schnider) and the other group received propofol following the TCI model of Marsh (TCI-Marsh). A manual perfusion technique (MCI, n=30) was used in the control group. Depth of anesthesia was controlled using the bispectral index (BSI) which was adjusted to fall within the range of 40-55. Hemodynamics, extubation times and time of awaking, rate and quality of propofol dose adjustment, total drug requirements, costs, and quality of recovery were documented. The incidence of postoperative nausea and vomiting (PONV) as well as shivering and patient satisfaction were also documented. Demographics, hemodynamics and perioperative data did not differ between the groups. Propofol consumption within the first 60 min also showed no significant differences. In the course of extended anaesthesia, propofol consumption was significantly less in both TCI groups compared to the control group (MCI) and the TCI-Schnider group also showed less episodes of bradycardia. The necessity of propofol dose adjustment did not differ significantly between the TCI groups. Administration and consumption of anaesthesia co-medication (fentanyl, remifentanil, cisatracurium) did not differ between the groups. The investigated propofol administration procedures using the MCI or TCI techniques were safe and easy to handle under BIS monitoring. No differences were found concerning extubation times and time of awaking. During extended anaesthesia procedures (>60 min), propofol consumption was lower with both TCI techniques and thus costs could be saved.