The investigators study whether four equipotent combinations of propofol and remifentanil (as predicted by interaction models for "tolerance of laryngoscopy") result in identical haemodynamic conditions, independent of their relative different balance between the concentration of propofol and remifentanil.
In anesthesia, the synergistic interaction between hypnotics and opioids is applied daily to give adequate anesthesia and analgesia at significantly lower doses compared with the ones needed if only one drug was given to reach the same effect. A lot of research has been done to quantify these interactions with a focus on the desired effects (Tolerance of laryngoscopy, tolerance of shake and shout etc...), but the simultaneous interaction on the unwanted side effects is less well described. The response surface model of Bouillon et al. and other models predict combinations of propofol and remifentanil effect-site concentrations that lead to an equipotent desired effect. Due to the availability of the models, the anesthesiologists now could use the knowledge on interactions to target specific effects more accurately, using predefined equipotent combinations of drugs: for instance, a desirable 90% probability of tolerance of laryngoscopy (TOL90) in the population can be reached through either a high propofol/low remifentanil combination, but equally well through a low propofol-high remifentanil combination. However, at this time it is not known whether some of the combinations of propofol and remifentanil have a favorable hemodynamic stability compared to other equipotent combinations. The researcher in this study want to determine whether equipotent combinations of remifentanil and propofol (all deliberately selected to evoke 90% probability of "tolerance to laryngoscopy"), result in different effects on the undesired side effects of anesthetics, such as hemodynamic instability (hypotension, changes in heart rate or cardiac output), decreases in cerebral or tissue oxygenation (both measured with near infrared spectroscopy).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Masking
TRIPLE
Enrollment
87
Predicted TOL90% according to Bouillon model
TOL 90% according to the Bouillon interaction model
TOL 90% according to the Bouillon interaction model
University Medical Center Groningen
Groningen, Provincie Groningen, Netherlands
Blood pressure
Continuously stored on a laptop (systolic, diastolic and mean blood pressure over time) using a Philips Non Invasive Blood Pressure measurements every minute and a Nexfin monitor (continuous non invasive blood pressure measurement)
Time frame: From start drug till intubation which will take on average 15 minutes of measurement
Electro Encephalographic derived indices of anesthetic depth
Bispectral index, Wavelet Transformation (WAV) index, Quantium Consciousness Index (qCON), Quantium Nociception Index (qNOX) to observe whether multiple electroencephalographic derived depth of anesthesia indices indicate the same equipotent effect in all 4 groups. All these measures are unitless values that range between 100 (for a fully responsive condition) and 0 (for a fully unresponsive condition). All these measures are extracted from the same frontal electroencephalogram but use different composite mathematical algorithms to translate the cortical state in numbers. We want to observe whether these composite algorithms measure consistent behavior between groups. This outcome is mainly ment as hypothesis generating for future research.
Time frame: From start first drug till intubation, which will take on average 15 minutes of measurement
Cerebral and tissue oxygenation
Continuously stored oxygenation saturation measured in tissue and cerebral cortex as measured by Near Infrared Spectrum Analysis (Forsyth monitor) and Inspectra monitor. Comparing differences between 4 groups with ANOVA.
Time frame: From start drug till intubation, which will take on average 15 minutes of measurement
Heart rate
Difference in median/mean heart rate to determine differences between 4 groups with ANOVA.
Time frame: From start first drug till intubation, which will take on average 15 minutes of measurement
Probability of tolerance to laryngoscopy
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TOL 90% according to the Bouillon interaction model
During pharmacological steady state of propofol/remifentanil, a laryngoscopy will be performed by one researcher and response or tolerance of the stimulus will be observed. A positive response will be defined as any somatic movement, swallowing or coughing during three minutes after laryngoscopy was applied. Also a increase in heart rate or systolic blood pressure of more than 20% from baseline values (one minute before laryngoscopy) will be defined as a positive response. Through PROBIT analysis we can plot the probability of response to laryngoscopy (%) as a function of respectively propofol or remifentanil drug concentrations.
Time frame: one minute before laryngoscopy till three minutes after
Cardiac index
Non invasive estimation of Cardiac output and Cardiac index patterns through the Nexfin monitor. Determine the differences between groups through ANOVA.
Time frame: From start first drug till intubation, which will take on average 15 minutes of measurement