REAL-TIME BEDSIDE MONITORING OF BLOOD PROPOFOL CONCENTRATIONS:

A method to determine blood concentrations of propofol is desirable to improve the safety and adjust anesthetic depth. The ability to monitor the blood concentration of propofol in real time would allow us to better titrate and provide adequate anesthesia throughout a surgical procedure. While real time monitoring of inhaled anesthetic concentration is a standard of care there is until now no equivalent commercially available system for the measurement of propofol. Current validated methods of analysis are laboratory based assays requiring considerable time for sample preparation and analysis. These are suitable for population pharmacokinetic studies, but the slow turnaround time of such tests preclude there application to real time management of patients. Estimations of blood propofol concentration from expired gases has yet to demonstrate consistent and reliable results.
Sphere Medical (Cambridge UK) has introduced the Pelorus 1000 propofol measurement system, which has been designed for rapid analysis of propofol concentration in whole blood samples. A sample of 0.7 ml is required and the whole blood propofol concentration is determined in approximately 5 min. The measurement technology used in the Pelorus is based on quantitative colorimetric principle.
The system has been shown to fulfill the requirements for measurement of propofol concentration in whole blood samples with precision and accuracy suitable for elucidating propofol pharmacokinetics at clinical relevant concentration with no requirement for sample preparation and a fast time to results. The analysis offers the opportunity to study propofol blood concentrations in real time at the bedside of the patient

8-jun-2015: Changes in hypothesis, inclusion criteria, intervention, primary outcome, secondary outcome and timepoints.

1) The aim of this study will be to prospectively test the validity of the Pelorus-Rapid-Propofol-Measurement-system (Sphere Medical) during TIVA anaesthesia.

2) Assesment of interference between propofol bloodconcentrations and sufentanil.

3) Assessment of gender influence on propofol concentration.

Arterial blood samples for propofol concentration determinations will be taken at the following timepoints:

1) Baseline

2) After start propofol every 5' during first 15 minutes

3) Every 15' until 1 hour after induction

4) Every 30 minutes till two hours after end of propofol TCI

Part I: A comparison of blood propofol concentrations during a TCI administration of a 1% or 2% formulation of propofol during intracranial neurosurgery/thyroid surgery/ear surgery
I.V. line for propofol and remifentanil/sufentanyl.
Remifentanil target controlled infusion Administration of remifentanil: set blood target Cp at desired concentration ( 0.2 ng/ml to start) or sufentanyl TCI (Start at 0,3ng/ml).



Administration of propofol: set target Cp at 4 µg/ml blood concentration. (Alaris PK pump, PK model Marsh/Schnider).



Intubation and ventilation.



During thyroid surgery, hypnotic effects are monitored using Neurosense monitoring (Neurowave systems) and propofol TCI is adapted to hold BIS between 40 and 60. Analgesic effects are monitored using A.N.I monitoring. Sufentanyl TCI is adapted to hold A.N.I. between 50 and 70.



During neurosurgery and ear/breast surgery, depth of anesthesia will be assessed by the haemodynamic and autonomic responses to surgical stimulation i.e.:

• An increase of systolic blood pressure > 20% from postinduction baseline value

• An increase of heart rate > 20% fom postinduction baseline value

Monitoring of vital signs (SBP, DBP, MAP, HR and SaO2). continue invasive blood-pressure and cardiac output will be assessed with the Flo-Trac (Edwards lifescience)



Part II: Influence of opioid supplementation with sufentanil or remifentanil on the real time blood concentrations of propofol during TCI.