Vasopressors and Inotropes: Phenylephrine, Ephedrine, Norepinephrine, Epinephrine, Vasopressin
CA-1 · intraoperative teaching CA-1 Bootcamp day 2. Authored from cited abstracts; every claim carries a PMID.
THE QUESTIONWhere the evidence disagrees
This topic was selected because an evidence synthesis beats a textbook on it: the trials disagree, or the guidance has moved recently.
THE EVIDENCE
What each source contributes, and how strong it is
Study design first — a cohort and a randomised trial do not carry the same weight.
Design
Year
Journal
What it found
Other
2024
Anaesthesia
Phenylephrine raises blood pressure while simultaneously reducing cardiac output
Other
2015
Anesthesiology
Norepinephrine carries weak beta-adrenergic activity alongside its potent alph
Other
2017
Anesthesiology
In a graded dose-response study the ED50 for restoring blood pressure was 10 m
Other
2003
Anesthesia and Analgesia
Ephedrine's pressor effect in vivo comes from releasing stored norepinephrine
Other
2005
Netherlands Journal of Medicine
Vasopressin raises mean arterial pressure through V1 receptors and lowers card
Other
2021
Journal of Anesthesia
Adrenaline is the first-line treatment for anaphylaxis and should be given int
8 resolved citations behind this deck; every point above traces to one of them.
IN PRACTICE
What the cohorts and reviews add
6 findings, each on the slide that follows.
Anaesthesia 2024
Phenylephrine raises blood pressure while simultaneously reducing cardiac output
Phenylephrine raises blood pressure while simultaneously reducing cardiac output
Anesthesiology 2015
Norepinephrine carries weak beta-adrenergic activity alongside its potent alph
Norepinephrine carries weak beta-adrenergic activity alongside its potent alpha effect
Anesthesiology 2017
In a graded dose-response study the ED50 for restoring blood pressure was 10 m
In a graded dose-response study the ED50 for restoring blood pressure was 10 micrograms of norepinephrine against 137 micrograms of phenylephrine, so…
Anesthesia and Analgesia 2003
Ephedrine's pressor effect in vivo comes from releasing stored norepinephrine
Ephedrine's pressor effect in vivo comes from releasing stored norepinephrine out of sympathetic nerve terminals rather than from direct receptor…
IN PRACTICE
Phenylephrine raises blood pressure while simultaneously reducing cardiac output
Other · Anaesthesia
Phenylephrine raises blood pressure while simultaneously reducing cardiac output, and although it increases cerebral blood flow it lowers cerebral tissue oxygen saturation - so the number on the monitor improves while the flow behind it does not.
Norepinephrine carries weak beta-adrenergic activity alongside its potent alph
Other · Anesthesiology
Norepinephrine carries weak beta-adrenergic activity alongside its potent alpha effect, and given by infusion at caesarean delivery it held systolic pressure as well as phenylephrine while preserving a greater cardiac output.
Ngan Kee et al., Anesthesiology 2015 · PMID 25635593
IN PRACTICE
In a graded dose-response study the ED50 for restoring blood pressure was 10 m
Other · Anesthesiology
In a graded dose-response study the ED50 for restoring blood pressure was 10 micrograms of norepinephrine against 137 micrograms of phenylephrine, so these two drugs can never be exchanged at the same numerical dose.
Ephedrine's pressor effect in vivo comes from releasing stored norepinephrine
Other · Anesthesia and Analgesia
Ephedrine's pressor effect in vivo comes from releasing stored norepinephrine out of sympathetic nerve terminals rather than from direct receptor activation, since destroying those terminals abolished the response, and in obstetric practice ephedrine has the highest probability of being the worst agent for fetal acid-base status.
Kobayashi et al., Anesthesia and Analgesia 2003 · PMID 14570629
IN PRACTICE
Vasopressin raises mean arterial pressure through V1 receptors and lowers card
Other · Netherlands Journal of Medicine
Vasopressin raises mean arterial pressure through V1 receptors and lowers cardiac output, has little effect in a healthy subject but potentiates norepinephrine in vasodilatory shock, and above 0.04 units per minute has been reported to cause cardiac arrest.
den Ouden et al., Netherlands Journal of Medicine 2005 · PMID 15719846
IN PRACTICE
Adrenaline is the first-line treatment for anaphylaxis and should be given int
Other · Journal of Anesthesia
Adrenaline is the first-line treatment for anaphylaxis and should be given intravenously in the perioperative setting, and anaphylaxis is exactly what you should suspect when hypotension persists despite inotropes and vasopressors even with no rash to look at.
Takazawa et al., Journal of Anesthesia 2021 · PMID 34651257
IN THE ROOM
What this changes about the next case
Colour is the strength of the evidence behind each step, not the urgency.
1
1
Phenylephrine raises blood pressure while simultaneously reducing cardiac output, and although it increases cerebral blood flow it lowers cerebral tissue oxygen saturation - so the number on the monitor improves while the flow behind it does not.
2
2
Norepinephrine carries weak beta-adrenergic activity alongside its potent alpha effect, and given by infusion at caesarean delivery it held systolic pressure as well as phenylephrine while preserving a greater cardiac output.
3
3
In a graded dose-response study the ED50 for restoring blood pressure was 10 micrograms of norepinephrine against 137 micrograms of phenylephrine, so these two drugs can never be exchanged at the same numerical dose.
4
4
Ephedrine's pressor effect in vivo comes from releasing stored norepinephrine out of sympathetic nerve terminals rather than from direct receptor activation, since destroying those terminals abolished the response, and in obstetric practice ephedrine has the highest probability of being the worst agent for fetal acid-base status.
5
5
Vasopressin raises mean arterial pressure through V1 receptors and lowers cardiac output, has little effect in a healthy subject but potentiates norepinephrine in vasodilatory shock, and above 0.04 units per minute has been reported to cause cardiac arrest.
The oral-boards stem on the next slide puts these into one scenario.
KEY TAKEAWAYS
What to carry into the next case
Phenylephrine raises blood pressure while simultaneously reducing cardiac output
Anaesthesia 2024
Norepinephrine carries weak beta-adrenergic activity alongside its potent alph
Anesthesiology 2015
In a graded dose-response study the ED50 for restoring blood pressure was 10 m
Anesthesiology 2017
Ephedrine's pressor effect in vivo comes from releasing stored norepinephrine
Anesthesia and Analgesia 2003
Choose the pressor by the receptor you actually need - squeeze the vessels, drive the heart, or both - and never forget that raising the pressure is not the same as raising the flow.
Questions I'll ask you in the room
Which of these raises blood pressure while lowering cardiac output, and when is that trade worth making?
She is bradycardic as well as hypotensive - does that change your first choice, and why?
Ephedrine worked the first two times and did nothing the third time. What happened?
The patient takes an ACE inhibitor and phenylephrine is not holding her. What else is in the drawer, and why might it work when phenylephrine will not?
Oral boards stem
Ten minutes into a laparoscopic hysterectomy in a healthy 45-year-old, the cuff reads 78/44 with a heart rate of 58. The drug drawer beside you holds phenylephrine, ephedrine, norepinephrine, epinephrine and vasopressin. Before you pick one up, your attending asks you to say out loud what each of them does to heart rate, to systemic vascular resistance, and to cardiac output.
The bottom lineChoose the pressor by the receptor you actually need - squeeze the vessels, drive the heart, or both - and never forget that raising the pressure is not the same as raising the flow.
Sources
[1] Meng et al., Anaesthesia 2024 · PMID 37948131 open
[2] Ngan Kee et al., Anesthesiology 2015 · PMID 25635593 open
[3] Ngan Kee, Anesthesiology 2017 · PMID 28872480 open
[4] Kobayashi et al., Anesthesia and Analgesia 2003 · PMID 14570629 open
[5] Singh et al., British Journal of Anaesthesia 2020 · PMID 31810562 open
[6] den Ouden et al., Netherlands Journal of Medicine 2005 · PMID 15719846 open
[7] Takazawa et al., Journal of Anesthesia 2021 · PMID 34651257 open
[8] Ma et al., Canadian Journal of Anaesthesia 2025 · PMID 40244358 open