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Updated: Jan 7, 2026
Quantifying Acute Changes in Renal Sympathetic Nerve Activity in Response to Central Nervous System Manipulations in Anesthetized Rats
Published on: September 11, 2018
The dose-response relationship between norepinephrine dose and mean arterial pressure with and without general
Ilonka N de Keijzer1, Johannes P van den Berg, Dario Massari
1From the Department of Anesthesiology, University Medical Center Groningen, University of Groningen, The Netherlands (INdK, JPvdB, DM, ARA, DJB, TWLS, MMRFS, PJC, JJV), Department of Laboratory Medicine, University Medical Center Groningen, University of Groningen, The Netherlands (MvF), Department of Basic and Applied Medical Sciences, Ghent University, Gent, Belgium (MMRFS).
Background:
Norepinephrine is commonly used to optimise arterial blood pressure during anaesthesia, yet data on its dose-response relationship are limited. Furthermore, the influence of general anaesthesia on this relationship is not well understood.
Objectives:
To examine the dose-response relationship between norepinephrine dose and mean arterial pressure (MAP) in healthy volunteers with and without general anaesthesia.
Design:
Observational healthy volunteer study.
Setting:
Tertiary university medical centre.
Participants:
Thirty-six healthy volunteers aged 18 to 70 years.
Interventions:
Norepinephrine infusion was initiated at 0.04 μg kg -1 min -1 and increased in four equal increments to 0.20 μg kg -1 min -1 , each lasting 15 min. After a washout period, anaesthesia was induced and maintained with propofol/remifentanil, and the norepinephrine infusion protocol was repeated. Surgical stimuli were simulated using intermittent 30-s tetanic electrical stimulus.
Main Outcome Measures:
The primary endpoint was the dose-response relationship between norepinephrine dose or plasma concentration and MAP. Secondary outcomes included other haemodynamic variables such as heart rate and cardiac index.
Results:
Norepinephrine dose-response models outperformed concentration-response models. The slope of the dose-MAP relationship was 103 (95% confidence interval (CI): 81 to 124) mmHg μg -1 kg min during the awake phase. After induction, MAP decreased by 34 mmHg (95% CI: -37 to -31) from 88 mmHg (95% CI: 85 to 91) and slope increased by 119 (95% CI: 119 to 120) mmHg μg -1 kg min during anaesthesia ( P < 0.001 difference in slopes and intercepts; cumulative slope equals approximately 222 mmHg μg -1 kg min). Norepinephrine requirement under anaesthesia can be calculated as ((target MAP - 54)/222) μg kg -1 min -1 .
Conclusions:
Linear models accurately described norepinephrine dose-response relationships in healthy volunteers in a simulated surgical environment, with a steeper slope observed during general anaesthesia. This relationship allows for a simple equation to estimate the required norepinephrine dose for a target blood pressure, although clinical observation and titration remain essential.
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