Unravelling the interplay between norepinephrine and propofol / remifentanil for maintaining adequate blood pressure under general anaesthesia: a PKPD-informed dose finding study in healthy volunteers

anesthesia pharmacodynamics Blood pressure

Prof. dr. M.M.R.F. Struys
J.J. Vos
Drs. J.P. van den Berg
I.N. de Keijzer
dr. P. Colin

Nature of the research:
Prospective healthy volunteer study

Fields of study:
anesthesiology pharmacology intensive care

Background / introduction
Intraoperative hypotension is an important risk-factor for the development of renal, myocardial and cerebral complications following surgery. Therefore, vasopressors, such as norepinephrine, are commonly used for maintaining or restoring arterial blood pressure (ABP) during general anesthesia. There is however surprisingly little information on the dose-response of norepinephrine, both in awake patients, and in patients under general anesthesia. Also, the administration of norepinephrine is reactive, i.e. follows when hypotension has already occurred, and should ideally be proactive, i.e. to prevent hypotension from developing, ultimately minimizing the risk of postoperative organ injury. In this study, the pharmacokinetic (PK) characteristics, as well as the pharmacodynamic (PD) characteristics of norepinephrine will be assessed in healthy volunteers during awake conditions and during a steady-state standardized general anesthesia using target-controlled infusions of propofol and remifentanil.
Research question / problem definition
To assess the effect of the administration of norepinephrine on ABP while subjects are awake and subsequently, to study the effects of the interactions of norepinephrine and anesthetics (propofol and remifentanil) on ABP under steady-state conditions during general anesthesia.
In this study, the student will be allowed the possibility to actively participate in the ongoing data collection during the experiments. This may include the drawing of arterial blood samples and the subsequent processing of these blood samples. Also, the student may assist in (digital) data recording and data analysis
1: Vos JJ, Scheeren TWL. Intraoperative hypotension and its prediction. Indian J Anaesth 2019, 63:877-885.
2: Beloeil H, Mazoit JX, Benhamou D, Duranteau J. Norepinephrine kinetics and dynamics in septic shock and trauma patients. Br J Anaesth 2005, 95:782-788.
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