Basisalgorithmus für „Point-of-Care“ basierte Hämotherapie

During perioperative treatment of coagulopathic patients the so-called Point-of-Care (POC) analyses enable more rapidly available and more comprehensive hemostatic analyses compared to routinely performed conventional coagulation testing, such as activated partial thromboplastin time (aPTT), international normalized ratio (INR), fibrinogen concentration and platelet count. In this review article a hemotherapy algorithm is presented which is based on viscoelastic and aggregometric POC measurements. The algorithm was designed double sided and consists of a general and a special part. The general part contains boxes and fields for sociodemographic data and gives general recommendations for coagulation management and therapy specifications for particular patient collectives and presents proposals for emergency reversal of anticoagulation therapy. The special part refers to basic physiological conditions for hemostasis and asks for measurement results of clot initiation, clot firmness, clot stability and platelet function analyses. Reference values were defined for each parameter and therapeutic options are presented. In cases of persistent coagulopathy despite algorithm-conform therapy, the algorithm could be run through once again. Finally, the algorithm presents therapeutic options for an ultima ratio therapy approach.     

Application of Bispectral Index and Narcotrend index to the measurement of the electroencephalographic effects of isoflurane with and without burst suppression

BACKGROUND: The Narcotrend monitor (MonitorTechnik, Bad Bramstedt, Germany) has recently been introduced as an intraoperative monitor of anesthetic state, based on a classification scheme originally developed for visual assessment of the electroencephalogram. The authors compared the performance of the Narcotrend index (software version 4.0) to the Bispectral Index (BIS, version XP; Aspect Medical Systems, Natick, MA) as electroencephalographic measures of isoflurane drug effect during general anesthesia. METHODS: The authors observed 15 adult patients scheduled to undergo radical prostatectomy with a combined epidural-isoflurane general anesthesia technique. At least 45 min after induction of general anesthesia, during a phase of constant surgical stimulation, end-tidal isoflurane concentrations were varied between 0.5 and 2.0 multiples of minimum alveolar concentration, and the BIS and the Narcotrend index were recorded. The prediction probability (PK) was calculated for the BIS and the Narcotrend index to predict isoflurane effect compartment concentration for each measure. The correlation analysis of the BIS and the Narcotrend index with the isoflurane effect compartment concentration was obtained by pharmacodynamic modeling based on two sigmoidal curves to account for the discontinuity in both indices with the onset of burst suppression. RESULTS: The prediction probabilities were indistinguishable (BIS PK = 0.72 +/- 0.07 (mean +/- SD); range, 0.61-0.84; Narcotrend index PK = 0.72 +/- 0.10; range, 0.51-0.87), as were the correlations between the electroencephalographic measures and isoflurane effect compartment concentrations (BIS R = 0.82 +/- 0.12; Narcotrend index R = 0.85 +/- 0.09). The pharmacodynamic models for the BIS and the Narcotrend index yielded nearly identical results. CONCLUSIONS: The BIS and the Narcotrend index detected the electroencephalographic effects of isoflurane equally. Combining two fractional sigmoid Emax models adequately described the data before and after the onset of burst suppression.     

Bispektralindex und Desflurankonzentration unter 1 MAC

ZusammenfassungFragestellung Kenntnisse des Zusammenhangs zwischen Bispektralindex (BIS, A-2000, Aspect Medical Systems, USA) und endtidaler Desflurankonzentration bei remifentanilbasierter Anästhesie liegen nicht vor. Wir untersuchten Desflurankonzentrationen unterhalb von 1 MAC (minimal alveolar concentration), da bei Fast-track-Anästhesie mit Remifentanil höhere Desflurandosierungen nicht erforderlich sind.Methodik Die Untersuchung erfolgte mit Zustimmung der Ethikkommission und dem schriftlichen Einverständnis von 50 orthopädischen Patienten. Die BIS-Elektrode (BIS-Sensor^TM, Aspect Medical Systems, USA) wurde wie vom Hersteller empfohlen auf der Stirn der Patienten befestigt. Nach oraler Prämedikation mit Diazepam 0,15 mg/kg abends und morgens wurde die Anästhesie mit 0,4 µg/kg/min Remifentanil und 2 mg/kg Propofol eingeleitet; nach orotrachealer Intubation erhielten alle Patienten standardisiert 0,2 µg/kg/min Remifentanil, während Desfluran in einem O₂-Luft-Gemisch nach klinischen Kriterien dosiert wurde. Nach der letzten Hautnaht wurde die Desfluran-Remifentanil-Zufuhr gestoppt und der Frischgasfluss auf 10 l/min O₂ erhöht; die maschinelle Beatmung wurde unverändert weitergeführt. Die endtidalen Desflurankonzentrationen und die BIS-Werte wurden während der Operation 5-minütlich und nach Operationsende minütlich als Datenpaare registriert. Anschließend wurden die intraoperativen Datenpaare für jeden Patienten mit der linearen Regression analysiert. Für die Datenpaare während der Ausleitung wurden die Desfluraneffektkompartimentkonzentrationen simuliert; die Korrelationsanalyse erfolgte mit einem sigmoidalen Modell.Ergebnisse Insgesamt wurden 1.483 Datenpaare bei 50 orthopädischen Patienten (44±13 Jahre, x±SD) erfasst. Die abhängig von publizierten BIS-Bereichen gemessenen mittleren Desflurankonzentrationen waren signifikant unterschiedlich: Im BIS-Bereich von 100–85 lag die Desflurankonzentration bei 1,1±0,7 Vol.-%, bei BIS-Werten von 84–65 bei 1,5±1,2 Vol.-%, bei BIS-Werten von 64–50 bei 2,9±1,3 Vol.-% und bei BIS-Werten von 49–40 bei 3,1±0,9 Vol.-% (ANOVA; p<0,05). Der Regressionskoeffizient zwischen BIS-Werten und endtidaler Desflurankonzentration lag für die intraoperativen Werte bei R=0,42±0,24 (Spannweite 0,05–0,96) und für die Datenpaare während der Ausleitung bei R=0,84±0,12 (Spannweite 0,61–0,99).Schlussfolgerung Veränderungen der Desflurankonzentration unterhalb von 1 MAC werden vom BIS-Monitor erkannt und klassifiziert; dabei wird—bei Kombination mit Remifentanil – bei 0,5 MAC Desfluran annäherungsweise ein BIS-Wert zwischen 40 und 49 erreicht.Diese Arbeit ist Herrn Prof. Dr. med. R. Larsen zum 60. Geburtstag gewidmet.Ergebnisse dieser Untersuchung wurden teilweise auf der Jahrestagung der European Society of Anaesthesiologists, Euroanaesthesia 2002, in Nizza, Frankreich, vorgestellt.     

Impact of bispectral index monitoring on stress response and propofol consumption in patients undergoing coronary artery bypass surgery

BACKGROUND: Bispectral Index (BIS)-titrated administration allows a reduction of propofol infusion rates in patients undergoing surgery. Resulting differences in anesthetic depth might affect the stress response to surgery involving neural circuitry not reflected in the electroencephalogram. METHODS: Forty patients scheduled to undergo elective coronary artery bypass grafting receiving a background infusion of remifentanil (0.3 microg . kg . min) were anesthetized with intravenous propofol delivered by target-controlled infusion according to the Marsh pharmacokinetic model under BIS monitoring. In a randomized, prospective design, 20 patients received propofol at a target concentration of 3 microg/ml, whereas in 20 patients propofol was titrated to maintain a BIS value of 40-50. Plasma concentrations of propofol (by means of gas chromatography-mass spectrometry), epinephrine, norepinephrine (by means of high-pressure liquid chromatography), cortisol (by means of radioimmunoassay), and interleukins 6 and 10 (by means of enzyme-linked immunosorbent assay) were measured repeatedly throughout surgery. RESULTS: BIS monitoring allowed a 30% reduction of propofol infusion rates and a similar decrease in plasma propofol concentrations in the BIS group without affecting the stress response to surgery for the group mean. None of the patients reported awareness during a standardized interview. Interestingly, propofol-remifentanil anesthesia blunted the release of epinephrine and cortisol to bypass surgery completely even when the propofol infusion rate was reduced according to BIS values. CONCLUSIONS: Total intravenous anesthesia using propofol-remifentanil effectively attenuates the neurohumoral stress response to coronary bypass surgery involving cardiopulmonary bypass. Titration of propofol using BIS allows for significant reduction of propofol consumption, with only minor effects on stress response under these conditions.     

Accuracy of portable quantitative capnometers and capnographs under prehospital conditions

This study was designed to assess the pCO(2) accuracy of portable mainstream (Tidal Wave, Novametrix; Propaq 106, Protocol) and sidestream capnometers (Capnocheck 8200, BCI; Capnocount mini, Weinmann; NPB-75, Nellcor Puritan Bennett; SC-210, Pryon) with respect to international standards and preclinical emergency conditions. Measurements were performed under temperature conditions of +22 degrees C and -20 degrees C using dry gas mixtures with different CO(2) concentrations (STPD) and in patients ventilated with pure oxygen (BTPS). Accuracy presented to be between +1% (Capnocheck) and +12% (Propaq) (STPD) and between -0.4% (Capnocheck) and +11% (Tidal Wave) (BTPS). The measurements were affected by low ambient temperature only in the NPB-75 (+15%). Our results indicate that portable quantitative capnometers are able to fulfill accuracy requirements as requested by international standards but can be affected by changing ambient temperatures.     

Failure of Two Commercial Indexes and Spectral Parameters to Reflect the Pharmacodynamic Effect of Desflurane on EEG

Objective We compared two PK/PD models, one with and one without a plateau effect. Bispectral (BIS, Aspect Medical Systems, Natick, MA, version XP) and Narcotrend™ (NCT, MonitorTechnik, Bad Bramstedt, Germany, Version 4.0) indices were used as an electroencephalographic measure of desflurane drug effect. Methods With IRB approval and informed consent we investigated 20 adult patients scheduled for radical prostatectomy. At least 45 minutes after induction of general anaesthesia, end-tidal concentrations of desflurane was varied between 3 and 10 vol%. To evaluate the relationship between concentrations and EEG indices, two different pharmacodynamic models were applied: A conventional model based on a single sigmoidal curve, and a novel model based on two sigmoidal curves for BIS and NCT values with and without burst suppression. The parameters of the models␣were estimated by NONMEM V (GloboMax, Hanover, USA) by minimizing log likelihood. Statistical significance between the two models was calculated by the likelihood ratio test. Results The maximum end-tidal desflurane concentration during the two concentrations ramps was 10.0 ± 1.4 vol%. The mean BIS and NCT values decreased significantly but slightly with increasing end-tidal desflurane concentrations between 4 and 8 vol%. Therefore a two sigmoidal curves PK/PD model including a plateau describes the effects of desflurane on BIS and Narcotrend better than a single sigmoidal curve model. The difference between the log likelihood values of the new PK/PD model with two connected sigmoidal curves and the classical E _max model with one sigmoidal curve is 634 (P < 0.001) for the BIS monitor and 4089 (P < 0.001) for the NCT. Conclusions BIS and Narcotrend are not useful to differentiate pharmacodynamic changes in the EEG between 4 and 9 vol% desflurane. This study was presented in part at the American Society of Anesthesiologists meeting October 20, 2005 Atlanta. Kreuer S, Bruhn J, Ellerkmann R, Ziegeler S, Kubulus D, Wilhelm W. Failure of two commercial indexes and spectral parameters to reflect the pharmacodynamic effect of desflurane on EEG.     

Impact of Bispectral Index Monitoring on Stress Response and Propofol Consumption in Patients Undergoing Coronary Artery Bypass Surgery

Background: Bispectral Index (BIS)-titrated administration allows a reduction of propofol infusion rates in patients undergoing surgery. Resulting differences in anesthetic depth might affect the stress response to surgery involving neural circuitry not reflected in the electroencephalogram.

Methods: Forty patients scheduled to undergo elective coronary artery bypass grafting receiving a background infusion of remifentanil (0.3 [mu]g [middle dot] kg-1 [middle dot] min-1) were anesthetized with intravenous propofol delivered by target-controlled infusion according to the Marsh pharmacokinetic model under BIS monitoring. In a randomized, prospective design, 20 patients received propofol at a target concentration of 3 [mu]g/ml, whereas in 20 patients propofol was titrated to maintain a BIS value of 40-50. Plasma concentrations of propofol (by means of gas chromatography-mass spectrometry), epinephrine, norepinephrine (by means of high-pressure liquid chromatography), cortisol (by means of radioimmunoassay), and interleukins 6 and 10 (by means of enzyme-linked immunosorbent assay) were measured repeatedly throughout surgery.

Results: BIS monitoring allowed a 30% reduction of propofol infusion rates and a similar decrease in plasma propofol concentrations in the BIS group without affecting the stress response to surgery for the group mean. None of the patients reported awareness during a standardized interview. Interestingly, propofol-remifentanil anesthesia blunted the release of epinephrine and cortisol to bypass surgery completely even when the propofol infusion rate was reduced according to BIS values.     

Quantification of exhaled propofol is not feasible during single-lung ventilation using double-lumen tubes: A multicenter prospective observational trial

Background

Volatile propofol can be measured in exhaled air and correlates to plasma concentrations with a time delay. However, the effect of single-lung ventilation on exhaled propofol is unclear. Therefore, our goal was to evaluate exhaled propofol concentrations during single-lung compared to double-lung ventilation using double-lumen tubes.

Methods

In a first step, we quantified adhesion of volatile propofol to the inner surface of double-lumen tubes during double- and single-lumen ventilation in vitro. In a second step, we enrolled 30 patients scheduled for lung surgery in two study centers. Anesthesia was provided with propofol and remifentanil. We utilized left-sided double-lumen tubes to separately ventilate each lung. Exhaled propofol concentrations were measured at 1-min intervals and plasma for propofol analyses was sampled every 20 min. To eliminate the influence of dosing on volatile propofol concentration, exhalation rate was normalized to plasma concentration.

Results

In-vitro ventilation of double-lumen tubes resulted in increasing propofol concentrations at the distal end of the tube over time. In vitro clamping the bronchial lumen led to an even more pronounced increase (Δ AUC +62%) in propofol gas concentration over time. Normalized propofol exhalation during lung surgery was 31% higher during single-lung compared to double-lung ventilation.

Conclusion

During single-lung ventilation, propofol concentration in exhaled air, in contrast to our expectations, increased by approximately one third. However, this observation might not be affected by change in perfusion-ventilation during single-lung ventilation but rather arises from reduced propofol absorption on the inner surface area of the double-lumen tube. Thus, it is only possible to utilize exhaled propofol concentration to a limited extent during single-lung ventilation.

Registration of Clinical Trial

DRKS-ID DRKS00014788 ( www.drks.de ).     

Comparison of BIS and AAI as measures of anaesthetic drug effect during desflurane-remifentanil anaesthesia

BACKGROUND: Autoregressive modelling with exogenous input of the middle-latency auditory evoked potential has been developed for monitoring of anaesthetic depth. This study was designed to investigate the dose-response relationship between endtidal desflurane concentrations and the Alaris Autoregressive Index (AAI, Alaris Medical, Hampshire, UK, version 1.4) or the bispectral index (Aspect Medical Systems, Newton, MA, USA, version XP). METHODS: Twenty-one patients scheduled for radical prostatectomy were investigated. After premedication and induction of anaesthesia with propofol und remifentanil all patients received atracurium and a remifentanil background infusion at a constant rate of 0.1 micro g kg(-1) min(-1). During dissection of the prostate, desflurane endtidal concentrations were varied between 3 and 9 vol%. Both AAI and BIS were determined and compared with the respective endtidal desflurane concentration. RESULTS: None of the patients showed a significant change of AAI values while changing the desflurane concentrations between 3 and 9 vol%. The dose-response of BIS values and desflurane concentrations was not uniform: two patients showed increasing BIS values with increasing desflurane concentrations, while in three patients BIS values remained unchanged. In 16 patients decreasing BIS values adequately reflected an increase in desflurane concentrations. CONCLUSION: Changes of desflurane concentrations during deep anaesthesia were adequately displayed only in 16 of 21 cases by BIS but in none of the cases by AAI monitoring.