From the FDA Drug Label
CLINICAL PHARMACOLOGY Mechanism of Action Metoprolol is a beta 1-selective (cardioselective) adrenergic receptor blocker. The mechanism of the antihypertensive effects of beta-blocking agents has not been fully elucidated However, several possible mechanisms have been proposed: (1) competitive antagonism of catecholamines at peripheral (especially cardiac) adrenergic neuron sites, leading to decreased cardiac output; Animal and human experiments indicate that metoprolol slows the sinus rate and decreases AV nodal conduction
The consequences of administering Lopressor (metoprolol) while on a norepinephrine (noradrenaline) infusion are:
- Decreased cardiac output: due to competitive antagonism of catecholamines at peripheral adrenergic neuron sites
- Reduced heart rate: as metoprolol slows the sinus rate
- Decreased AV nodal conduction: which can lead to a decrease in cardiac contractility The administration of metoprolol with norepinephrine infusion may counteract the effects of norepinephrine, leading to decreased cardiac output and reduced blood pressure 1.
From the Research
Administering Lopressor (metoprolol) while on a norepinephrine infusion can lead to severe hypotension, bradycardia, and cardiovascular collapse, and therefore, immediate action should be taken to monitor the patient closely and adjust the norepinephrine infusion rate as needed. The interaction between metoprolol and norepinephrine is concerning because norepinephrine primarily works through alpha-adrenergic receptors to cause vasoconstriction, but also has some beta-receptor activity 2. Metoprolol blocks beta-1 receptors, potentially negating some of norepinephrine's cardiac effects and causing a mismatch between cardiac output and vascular tone. Some key points to consider in this situation include:
- Monitoring the patient closely for signs of hypotension, bradycardia, and cardiovascular collapse
- Notifying the physician immediately and checking vital signs frequently
- Considering stopping or reducing the norepinephrine infusion rate based on blood pressure readings
- Potential interventions for severe hypotension, such as IV fluids, positioning the patient with legs elevated, and administering medications like glucagon (3-10 mg IV) or epinephrine if hypotension is severe and unresponsive
- Documenting the medication error according to institutional protocol and continuing close monitoring until the patient is stable, typically for at least 4-6 hours given metoprolol's duration of action 3. It's also important to note that the response of cardiac output to norepinephrine can be predicted by baseline stroke volume variation, and that an increase in mean systemic filling pressure and a decrease in resistance for venous return can lead to an increase in cardiac output 4. However, the most recent and highest quality study on vasopressor therapy in the intensive care unit recommends norepinephrine as the first-line agent for septic shock, and emphasizes the importance of individualizing the mean arterial pressure target and adding vasopressin in case of shock refractory to norepinephrine 2.