The dose-response relationship between norepinephrine dose and mean arterial pressure with and without general anaesthesia: A study in healthy volunteers

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 kg-1 min-1). 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.