Walking the Isobole of Drug Interaction

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).

Inclusion criteria

• Written informed consent
• General anesthesia required for the procedure
• Age: 18 years and older
• American Society of Anesthesiologists (ASA) physical status I to III

Exclusion criteria

• Refusal to participate in this study
• Contra-indications for the use of propofol or remifentanil
• BMI > 35 kg/m2
• Central nervous system disorders (i.e. cerebrovascular accident, dementia, seizures, psychiatric disorders)
• Relevant hepatic disease (Child B or higher)
• Regular use of medication that affects the central nervous system (i.e. benzodiazepines, antidepressants, antipsychotics, antiepileptic drugs)
• Use of alpha-agonists or beta-blockers
• Overt signs of alcohol abuse
• Use of preoperative benzodiazepines (on the day of the study)
• Beta blockers eye drips
• Overt signs of Drugs abuse