None listed
Conditions
Brief summary
Response surface models are becoming increasingly prevalent in the anaesthetic literature. They have been shown to be useful in indentifying optimal drug dose combinations designed to achieve specific clinical outcomes. An example is the optimal combination of propofol and remifentanil required to tolerate esophageal instrumentation while maintaining spontaneous breathing. Additionally, these models can be used to predict patient wake up times at the end of anaesthesia, and have been implemented in novel anaesthetic display monitors. The latter is likely to improve drug titration for individual patients by promoting the active use of pharmacokinetic and pharmacodynamic knowledge in theatre. We believe that response surface models are potentially useful when combinations of drugs that are known to display synergistic interactions are given as infusions. Knowledge about drug interactions is commonly employed in anaesthesia, but rarely is it directly applied using pharmacodynamic models. Software is available that allows us to drive infusions based on interaction models using standard ADHB alaris infusion pumps. These models are extendable to three drug interactions. We wish to conduct a ‘proof of concept’ study to validate our hypothesis that pharmacodynamic response surface models can be directly applied to administration of anaesthesia, and to assess the clinical feasibility of using these models in this context. We hypothesise that response surface model driven infusions will allow anaesthetists to target a level of drug effect (in this study Bispectral Index, or BIS, as a measure of depth of anaesthesia) while varying the ratio of propofol:remifentanil. This would be a useful tool in anaesthesia where the ratio of hypnotic:opioid is often varied depending on the particular needs of individual patients, but manual targeting of effect levels such as BIS is often difficult.
Interventions
Current automated methods to infuse anaesthetic drugs are reliant on pharmacokinetic models. These models target plasma concentrations and do not account for interactions between drugs. We will conduct a proof of concept study to evaluate the use of linked pharmacokinetic - pharmacodynamic models for infusion of anaesthetic drugs. The study model will target effect (as Bispectral Index, or BIS monitoring) and will account for interactions between anaesthetic drugs. Propofol and remifentanil will
Current automated methods to infuse anaesthetic drugs are reliant on pharmacokinetic models. These models target plasma concentrations and do not account for interactions between drugs. We will conduct a proof of concept study to evaluate the use of linked pharmacokinetic - pharmacodynamic models for infusion of anaesthetic drugs. The study model will target effect (as Bispectral Index, or BIS monitoring) and will account for interactions between anaesthetic drugs. Propofol and remifentanil will be given as study drugs. Only patients who were to receive these agents as part of their standard anaesthetic care will be recruited. Doses of propofol and remifentanil will be within the normal range of standard care - the dose given during total intravenous anaesthesia (TIVA) for both drug varies with patient requirements during normal practice and this will also be the case in this study. For the purposes of the study, we will be interested in the ratio of propofol dose to remifentanil dose. Standard procedure for administration of TIVA using propofol and remifentanil is via pharmacokinetic based infusion pump. In this situation anaesthetists select a target plasma or effect site concentration. Although the same pumps will be used, the pumps themselves will be driven by external software from a study designated laptop and drug infused as per a pharmacodynamic response surface model. Anaesthetists will instead select a target BIS level. All patients will receive BIS monitoring as part of the study protocol. This is already considered standard monitoring in our hospital.All aspects of patient care will remain with the attending anaesthetist as is routine care. Patients will be studied only once, during their surgery.
Sponsors
University of Auckland
Study design
Allocation
Non-randomised trial
Primary purpose
Educational / counselling / training
Eligibility
Sex/Gender
All
Age
18 Years to 45 Years
Healthy volunteers
No
Inclusion criteria
Patients will be eligible if they are 1. American Society of Anesthesiologists physical status I and II, 2. aged 18-45 years, 3. scheduled for a general anaesthetic with endotrachael intubation and the use of muscle relaxants, 4. scheduled for elective surgery on Levels 4 and 8 of Auckland City Hospital.
Exclusion criteria
Patients will be excluded if they 1. have a history of chronic opioid consumption, 2. use psychoactive medication (including high alcohol intake), 3. have neurological dysfunction, 4. require premedication before surgery
Outcome results
None listed