Stefan Schraag

The performance of electroencephalogram bispectral index and auditory evoked potential index to predict loss of consciousness during propofol infusion.

UNLABELLED The bispectral index (BIS) of the electroencephalogram and middle latency auditory evoked potentials are likely candidates to measure the level of unconsciousness and, thus, may improve the early recovery profile. We prospectively investigated the predictive performance of both measures to distinguish between the conscious and unconscious state. Twelve patients undergoing lower limb orthopedic surgery during regional anesthesia additionally received propofol by target-controlled infusion for sedation. The electroencephalogram BIS and the auditory evoked potential index (AEPi), a mathematical derivative of the morphology of the auditory evoked potential waveform, were recorded simultaneously in all patients during repeated transitions from consciousness to unconsciousness. Logistic regression procedures, receiver operating characteristic analysis, and sensitivity and specificity were used to compare predictive ability of both indices. In the logistic regression models, both the BIS and AEPi were significant predictors of unconsciousness (P < 0.0001). The area under the receiver operating characteristic curve for discrete descending index threshold values was apparently, but not significantly (P > 0.05), larger for the AEPi (0.968) than for the BIS (0.922), indicating a trend of better discriminatory performance. We conclude that both the BIS and AEPi are reliable means for monitoring the level of unconsciousness during propofol infusion. However, AEPi proved to offer more discriminatory power in the individual patient. IMPLICATIONS Both the bispectral index of the electroencephalogram and the auditory evoked potentials index are good predictors of the level of sedation and unconsciousness during propofol infusion. However, the auditory evoked potentials index offers better discriminatory power in describing the transition from the conscious to the unconscious state in the individual patient.

Use of Target Controlled Infusion to Derive Age and Gender Covariates for Propofol Clearance

AbstractBackground and objective: Attempts to describe the variability of propofol pharmacokinetics in adults and to derive population covariates have been sparse and limited mainly to experiments based on bolus doses or infusions in healthy volunteers. This study aimed to identify age and gender covariates for propofol when given as an infusion in anaesthetized patients. Study design and setting: One hundred and thirteen patients (American Society of Anesthesiologists class I or II and aged 14–92 years) were anaesthetized for elective surgical procedures with propofol using a target controlled infusion (TCI) system and with alfentanil as a baseline analgesic infusion. Frequent venous blood samples were obtained for measurement of propofol plasma concentrations. Pharmacokinetic and statistical analysis: Pharmacokinetic accuracy was determined by the percentage prediction error, bias and precision, as were wobble and divergence. The clearance of propofol from the central compartment was determined for each patient using the computerized record of the infusion profile delivered to each patient, together with relevant blood propofol concentration estimations. For each patient, the nonlinear mixed-effects modelling (NONMEM) objective function was employed to determine the goodness of fit. Results: The population distribution of propofol clearance was subsequently found to have a Gaussian distribution only in the log domain (mean value equivalent to 26.1 mL/kg/min). The distribution in the normal domain was consequently asymmetric, with a slight predominance of patients with high values of clearance (5% and 95% confidence limits 17.7 and 42.1 mL/kg/min, respectively). Using regression analysis, gender and age covariates were derived that optimized the performance of the target controlled infusion system. The clearance (CL) of propofol in male patients changed little with age (CL [mL/kg/min] = 26.88 − 0.029 × Age; r2 = 0.006) whereas that in female patients had a higher initial value but decreased progressively with age (CL [mL/kg/min] = 37.87 − 0.198 × Age; r2 = 0.246). Conclusion: We achieved a relatively simple and practical covariate model in which the variability of pharmacokinetics within the study population could be ascribed principally to variability in clearance from the central compartment. Pharmacokinetic simulation predicted an improved performance of the TCI system when employing the derived covariates model, especially in elderly female patients.

The contribution of remifentanil to middle latency auditory evoked potentials during induction of propofol anesthesia.

There is a debate regarding whether opioids, as a component of general anesthesia, are adequately reflected in the assessment of anesthesia based on derivatives of the electroencephalogram. To test the hypothesis of a possible quantitative contribution of remifentanil on middle latency auditory evoked potentials, we studied its interaction with propofol anesthesia in 45 unpremedicated male patients undergoing elective lower limb orthopedic surgery. They were allocated randomly to three groups. The first two groups received remifentanil either with a high (8 ng mL−1) or a low (3 ng mL−1 target concentration using target-controlled infusion (TCI). The third group received spinal anesthesia instead of remifentanil. Anesthesia was induced by a stepwise increase in propofol concentration using TCI. The auditory evoked potential index (AEPex) and calculated propofol effect site concentrations were determined at loss of consciousness and the reaction to laryngeal mask airway insertion was noted. The propofol infusion was then converted to a closed-loop TCI using an AEPex value of 40 as the target. We found no significant contribution of remifentanil alone on the auditory evoked response, whereas increasing concentrations of remifentanil led to a significant decrease of the calculated propofol effect site concentrations (P = 0.023) necessary for unconsciousness. Prediction probability for AEPex was inversely related to the remifentanil concentration and was best for the control group, which received propofol alone. These results support previous findings of a quantitative interaction between remifentanil and propofol for loss of consciousness but question the specific contribution of remifentanil to auditory evoked potentials.

Interoperator and Intraoperator Variability of Whole Blood Coagulation Assays: A Comparison of Thromboelastography and Rotational Thromboelastometry

OBJECTIVES Near-patient viscoelastic tests have proved useful in decreasing blood and blood product use in cardiac surgery. Two different analyzers are available, TEG and ROTEM. Many different individuals operate these devices, which raises concern that this factor may significantly affect results. The present study sought to objectively assess variability in results between operators. DESIGN Prospective study. SETTING Regional cardiac center. PARTICIPANTS Adult patients undergoing elective cardiac surgery. INTERVENTIONS Thirty-six mL of blood were taken from each of 21 patients. TEG kaolin and functional fibrinogen (FF) analyses and the equivalent ROTEM INTEM S and FIBTEM S analyses were performed. Six operators performed one of each test per patient to assess interoperator variability. One further operator performed 6 of each test per patient to assess intraoperator variability. MEASUREMENTS AND MAIN RESULTS All routine measurement parameters were noted and the coefficient of variation (CV) calculated, analyzing comparable parameters. All inter-operator CVs were significantly lower for ROTEM analyses compared with TEG. CV for INTEM S CT/ kaolin r time was 4.7 versus 16.3 and MCF/MA was 2.6 versus 4.3 (p < 0.01). Similarly, FIBTEM S MCF/ FF MA was 8.3 versus 12.2. All intraoperator CVs were significantly lower for ROTEM analyses compared with TEG (p<0.01). CV for INTEM S CT/kaolin r time was 3.1 versus 9.8 and MCF/ MA was 1.6 versus 4. Similarly, FIBTEM S MCF/ MA was 6.9 versus 12.1. CONCLUSIONS This series of results suggested ROTEM analyses are more reproducible than TEG and, consequently, that ROTEM may be better suited for use in a multiuser environment.

„Target controlled infusion“ (TCI) – ein Konzept mit Zukunft?

Over the last 10 years the technique of target-controlled infusion (TCI) has substantially influenced the development and practice of intravenous anaesthesia. It opened the possibility of many new and exciting applications of perioperative anaesthetic care. More recent and current developments, such as open TCI (target-controlled infusion) and the availability of generic anaesthetic agents combined with modern infusion pumps, means that TCI can become a standard procedure in anaesthesia and is no longer just a research tool for specialists and enthusiasts. This review explains the fundamentals and applications of intravenous drug delivery by TCI and gives practice guidelines to successfully implement the technique into clinical practice. The aim is to provide a comprehensive reference based on clinically proven evidence.

[Target-controlled infusion (TCI) - a concept with a future?: state-of-the-art, treatment recommendations and a look into the future]

Over the last 10 years the technique of target-controlled infusion (TCI) has substantially influenced the development and practice of intravenous anaesthesia. It opened the possibility of many new and exciting applications of perioperative anaesthetic care. More recent and current developments, such as open TCI (target-controlled infusion) and the availability of generic anaesthetic agents combined with modern infusion pumps, means that TCI can become a standard procedure in anaesthesia and is no longer just a research tool for specialists and enthusiasts. This review explains the fundamentals and applications of intravenous drug delivery by TCI and gives practice guidelines to successfully implement the technique into clinical practice. The aim is to provide a comprehensive reference based on clinically proven evidence.

„Target-controlled infusion“

Zusammenfassung„Target-controlled infusion“ (TCI) ist seit der kommerziellen Einführung im Jahr 1996 zu einer etablierten Applikationsform intravenöser Anästhetika geworden. Zusätzliche Optionen der modernen TCI-Systeme wie die Wahl zwischen unterschiedlichen Modellen und Applikationsmodi verkomplizieren allerdings den Gebrauch für den wenig erfahrenen Benutzer. Die vorliegende Übersicht beschreibt die Unterschiede der pharmakokinetischen Modelle, der Applikationsmodi und den Einfluss von Kovariaten sowie die Konsequenzen für die Dosierung mit dem Ziel, dem Benutzer von modernen TCI-Systemen die zugrunde liegenden wissenschaftlichen Konzepte und deren Bedeutung für die klinische Praxis zu vermitteln.AbstractSince its commercial introduction in 1996, target-controlled infusion (TCI) has become an established technique for administration of intravenous anaesthetics. Modern TCI systems, however, are characterized by an increasing number of additional options and features, such as the choice between different pharmacokinetic models and modes of application, which may confuse the less experienced user. This review describes the differences between pharmacokinetic models, modes of application and the effect of covariates as well as the consequences for dosing. The aim is to explicate for the user of modern TCI systems the underlying scientific concepts and the relevance for clinical practice.

The effective concentration 50 (EC50) for propofol with 70% xenon versus 70% nitrous oxide.

BACKGROUND: Xenon anesthesia has many favorable properties, such as pain modulation and organ protection. However, due to its MAC of 70%, it cannot be used as a sole anesthetic. We estimated the amount of propofol required to supplement xenon to produce adequate anesthesia in 50% and 95% of patients in comparison with nitrous oxide. METHODS: We randomized 75 premedicated female patients to receive either 70% xenon or 70% nitrous oxide in oxygen supplemented by propofol target-controlled infusion anesthesia starting with 4.5 &mgr;g/mL for the first patient in each group. Dixons up and down method was used to determine the propofol concentration for subsequent patients. After induction of anesthesia with propofol, patients breathed 70% xenon or 70% nitrous oxide in oxygen via a facemask for 15 min. They were then observed for movement in response to skin incision for 60 s after the incision and assigned as movers or nonmovers. Probit analysis was used to estimate the effective concentration 50% and 95% (EC50 and EC95) for propofol in both groups. RESULTS: The EC50 for propofol with 70% xenon was1.5&mgr;g/mL and the EC95 was 2.3 &mgr;g/mL. The EC50 and EC95 values for propofol with nitrous oxide were 2.2 and 8.2 &mgr;g/mL, respectively. This implies a reduction of propofol requirements between 32% (EC50) and 72% (EC95) by xenon compared with nitrous oxide. The suppression of auditory evoked potentials was more pronounced with xenon than with nitrous oxide. CONCLUSION: Xenon seems to be clinically more potent than nitrous oxide, but still requires minimal supplement of a hypnotic anesthetic to suppress noxious stimulation during and after skin incision.

[Target-controlled infusion. Clinical relevance and special features when using pharmacokinetic models]

Zusammenfassung„Target-controlled infusion“ (TCI) ist seit der kommerziellen Einführung im Jahr 1996 zu einer etablierten Applikationsform intravenöser Anästhetika geworden. Zusätzliche Optionen der modernen TCI-Systeme wie die Wahl zwischen unterschiedlichen Modellen und Applikationsmodi verkomplizieren allerdings den Gebrauch für den wenig erfahrenen Benutzer. Die vorliegende Übersicht beschreibt die Unterschiede der pharmakokinetischen Modelle, der Applikationsmodi und den Einfluss von Kovariaten sowie die Konsequenzen für die Dosierung mit dem Ziel, dem Benutzer von modernen TCI-Systemen die zugrunde liegenden wissenschaftlichen Konzepte und deren Bedeutung für die klinische Praxis zu vermitteln.AbstractSince its commercial introduction in 1996, target-controlled infusion (TCI) has become an established technique for administration of intravenous anaesthetics. Modern TCI systems, however, are characterized by an increasing number of additional options and features, such as the choice between different pharmacokinetic models and modes of application, which may confuse the less experienced user. This review describes the differences between pharmacokinetic models, modes of application and the effect of covariates as well as the consequences for dosing. The aim is to explicate for the user of modern TCI systems the underlying scientific concepts and the relevance for clinical practice.

Mobile computing in anaesthesiology and intensive care medicine. The practical relevance of portable digital assistants

Zusammenfassung“Taschencomputer” oder auch PDAs (“portable digital assistants”) können in der heutigen Zeit für den Anästhesisten und Intensivmediziner von großem Wert sein. Die Entwicklung in der Medizin geht kontinuierlich in Richtung “bedside computing”. Kleine portable Geräte stehen in unterschiedlichen Ausführungen zur Verfügung. Zu jeder Zeit ist es dem Mediziner möglich, einen fast vollwertigen Computer bei sich zu tragen. Er ist Datenbank, Nachschlagewerk, Patientenverwaltung, Terminplaner, Rechner, Buch, Zeitschrift und vieles mehr in einem Gerät. Der PDA sorgt dafür, dass für die Arbeit notwendige Informationen jederzeit und überall schnell verfügbar sind. In dieser Übersicht sollen die Möglichkeiten für die Benutzung des PDA in Anästhesie und Intensivmedizin aufgezeigt werden. Entwicklungen in anderen Ländern, Möglichkeiten aber auch Probleme wie Datensicherheit und Netzwerktechnologie werden diskutiert.AbstractPortable digital assistants (PDAs) may be of value to the anaesthesiologist as development in medical care is moving towards “bedside computing”. Many different portable computers are currently available and it is now possible for the physician to carry a mobile computer with him all the time. It is data base, reference book, patient tracking help, date planner, computer, book, magazine, calculator and much more in one mobile device. With the help of a PDA, information that is required for our work may be available at all times and everywhere at the point of care within seconds. In this overview the possibilities for the use of PDAs in anaesthesia and intensive care medicine are discussed. Developments in other countries, possibilities in use but also problems such as data security and network technology are evaluated.