Experimental measurement of analgesia during anesthesia

Despite various efforts there is still the need for adequate monitoring of pain and nociception during anesthesia. In previous studies we measured pain responses during anesthesia based on single end‐points, eg heart rate, blood pressure and pulse transit time. None of these parameters provided sufficient
information regarding nociception. We therefore want to further investigate this matter using a composite parameter, the Nociception Level or NoL. The NoL is a novel index that measures the magnitude of the autonomic response to painful stimuli. The NoL combines information from several physiological parameters, which represent different autonomic pathways. This is a multi‐parameter approach empowered with state‐of‐the‐art
signal processing and machine learning techniques. The NoL has been shown to have strong association with intensity of the pain stimuli (see publications).

We hypothize that higher opioid doses will lead to a lower NOL.

Measurements will be performed just prior to 1) laryngoscopy (during and the 3‐min following) and 2) intubation. The same will be done for insertion of the 3) gastric tube (if applicable), 4) bladder catheter (if applicable) and 5) skin incision.

Study groups:
Group 1 (n = 12): PROPOFOL ONLY GROUP. In this study group measurements will be
obtained before intubation or opioid administration. To that end plasma propofol
concentration will be increased slowly from 0 to 4 μg/ml in steps of 0.5 μg/mL. After the
highest target is reached, the propofol target concentration will be lowered to get a BIS
value of 50. After 5‐min, the laryngoscope will be inserted into the mouth. Next the
laryngoscope will be removed. After 5‐min the laryngoscope will be placed again and the
patient will be intubated.
Group 2 (n = 12): PROPOFOL + REMIFENTANIL TARGET A. The subject will be intubated
according to the design of group 1. The propofol concentration will be 1‐2 μg/kg, aimed at a
BIS of 50, with 1 ng/ml remifentanil.
Group 3 (n = 12): PROPOFOL + REMIFENTANIL TARGET B. The subject will be intubated
according to the design of group 1. The propofol concentration will be 1‐2 μg/kg, aimed at a
BIS of 50, with 2 ng/ml remifentanil
Group 4 (n = 12): PROPOFOL + REMIFENTANIL TARGET C. The subject will be intubated
according to the design of group 1. The propofol concentration will be 1‐2 μg/kg, aimed at a
BIS of 50, with 3 ng/ml remifentanil.
Group 5 (n = 12): PROPOFOL + REMIFENTANIL TARGET D. The subject will be intubated
according to the design of group 1. The propofol concentration will be 1‐2 μg/kg, aimed at a
BIS of 50, with 4 ng/ml remifentanil.
Group 6 (n = 12): PROPOFOL + REMIFENTANIL TARGET E. The subject will be intubated
according to the design of group 1. The propofol concentration will be 1‐2 μg/kg, aimed at a
BIS of 50, with 5 ng/ml remifentanil.
Group 7 (n = 12): PROPOFOL + REMIFENTANIL TARGET C. The subject will be intubated
according to the design of group 1. The remifentanil target will be 3 ng/ml remifentanil. The
propofol concentration will aim a BIS of 30.
Group 8 (n = 12): PROPOFOL + REMIFENTANIL TARGET C. The subject will be intubated
according to the design of group 1. The remifentanil target will be 3 ng/ml remifentanil. The
propofol concentration will aim a BIS 70.
5
In Group 1‐6, propofol will be administered first to get a BIS of 50. Next remifentanil will be
added and the propofol value will be altered such that BIS remains 50.